U.S. patent application number 10/507502 was filed with the patent office on 2005-07-14 for broad -spectrum cephem compounds.
This patent application is currently assigned to SHIONOGI & CO., LTD.. Invention is credited to Nishitani, Yasuhiro, Yamano, Yoshinori.
Application Number | 20050153950 10/507502 |
Document ID | / |
Family ID | 28035247 |
Filed Date | 2005-07-14 |
United States Patent
Application |
20050153950 |
Kind Code |
A1 |
Nishitani, Yasuhiro ; et
al. |
July 14, 2005 |
Broad -spectrum cephem compounds
Abstract
A compound of the formula: 1 (wherein, T is S, SO or O; X is
halogen, CN, carbamoyl optionally substituted with lower alkyl,
lower alkyl, lower alkoxy, or lower alkylthio; A is substituted
lower alkylene (wherein the substituent is optionally substituted
mono lower alkyl, optionally substituted lower alkylidene, or
optionally substituted lower alkylene); Z.sup.+ is an optionally
substituted, a cation and an N atom-containing heterocyclic group),
ester, amino-protected compound wherein the amino bonds to a
thiazole ring at the 7-position, or pharmaceutically acceptable
salt or solvate thereof.
Inventors: |
Nishitani, Yasuhiro;
(Osaka-shi, JP) ; Yamano, Yoshinori;
(Toyonaka-shi, JP) |
Correspondence
Address: |
FOLEY AND LARDNER
SUITE 500
3000 K STREET NW
WASHINGTON
DC
20007
US
|
Assignee: |
SHIONOGI & CO., LTD.
Osak-shi
JP
|
Family ID: |
28035247 |
Appl. No.: |
10/507502 |
Filed: |
September 13, 2004 |
PCT Filed: |
March 18, 2003 |
PCT NO: |
PCT/JP03/03249 |
Current U.S.
Class: |
514/202 ;
514/210.08; 540/222 |
Current CPC
Class: |
C07D 501/00 20130101;
A61P 31/04 20180101; A61K 31/546 20130101; C07D 501/56
20130101 |
Class at
Publication: |
514/202 ;
540/222; 514/210.08 |
International
Class: |
A61K 031/545; A61K
031/5383; C07D 501/14 |
Foreign Application Data
Date |
Code |
Application Number |
Mar 18, 2002 |
JP |
2002-073526 |
Claims
1. A compound of the formula: 259(wherein, T is S, SO or O; X is
halogen, CN, carbamoyl optionally substituted with lower alkyl,
lower alkyl, lower alkoxy, or lower alkylthio; A is substituted
lower alkylene (wherein the substituent is optionally substituted
mono lower alkyl, optionally substituted lower alkylidene, or
optionally substituted lower alkylene); Z.sup.+ is an optionally
substituted, a cation and an N atom-containing heterocyclic group),
ester, amino-protected compound wherein the amino bonds to a
thiazole ring at the 7-position, or pharmaceutically acceptable
salt or solvate thereof.
2. A compound according to claim 1, wherein T is S, ester,
amino-protected compound wherein the amino bonds to a thiazole ring
at the 7-position, or pharmaceutically acceptable salt or solvate
thereof.
3. A compound according to claim 1, wherein T is O, ester,
amino-protected compound wherein the amino bonds to a thiazole ring
at the 7-position, or pharmaceutically acceptable salt or solvate
thereof.
4. A compound according to claim 1, wherein X is halogen or lower
alkyl, ester, amino-protected compound wherein the amino bonds to a
thiazole ring at the 7-position, or pharmaceutically acceptable
salt or solvate thereof.
5. A compound according to claim 1, wherein A is of the formula:
260(wherein, R.sup.1 and R.sup.2 are different each other and
independently hydrogen or optionally substituted lower alkyl, or
taken together may form optionally substituted lower alkylidene or
optionally substituted lower alkylene.), ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate
thereof.
6. A compound according to claim 5, wherein A is a divalent group
of any of the following formulae, ester, amino-protected compound
wherein the amino bonds to a thiazole ring at the 7-position, or
pharmaceutically acceptable salt or solvate thereof. 261(wherein,
Me is methyl; Et is ethyl; i-Pr is isopropyl)
7. A compound according to claim 5 wherein R.sup.1 and R.sup.2 are
different each other and independently hydrogen or lower alkyl,
ester, amino-protected compound wherein the amino bonds to a
thiazole ring at the 7-position, or pharmaceutically acceptable
salt or solvate thereof.
8. A compound according to claim 5 wherein R.sup.1 and R.sup.2 are
different each other and independently hydrogen or methyl, ester,
amino-protected compound wherein the amino bonds to a thiazole ring
at the 7-position, or pharmaceutically acceptable salt or solvate
thereof.
9. A compound according to claim 5, wherein "---COOH" is a group of
the formula: 262ester, amino-protected compound wherein the amino
bonds to a thiazole ring at the 7-position, or pharmaceutically
acceptable salt or solvate thereof.
10. A compound according to claim 1 wherein Z.sup.+ is a saturated
or unsaturated, monocyclic or condensed cyclic, and one or more of
N atom-containing quarternary ammonium group of the formula:
263which may have 1 to 4 substituents, ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate
thereof.
11. A compound according to claim 1, ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate thereof,
wherein Z.sup.+ is a heterocyclic group of any one of the formulae:
264265(wherein, R.sup.3 and R.sup.4 each is independently hydrogen,
optionally substituted lower alkyl, optionally substituted
cycloalkyl, optionally substituted lower alkenyl, optionally
substituted amino, hydroxy, halogen, optionally substituted
carbamoyl, optionally substituted alkyloxy, or optionally
substituted heterocyclic group.)
12. A compound according to claim 1, ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate thereof,
wherein Z.sup.+ is a heterocyclic group of any one of the formulae:
266(wherein, R and R' each is independently hydrogen, lower alkyl,
amino, mono- or di- lower alkylamino, lower alkenyl, amino lower
alkyl, lower alkylamino lower alkyl, lower alkylamino lower
alkylamino, amino lower alkyloxyamino, amino substitute with
optionally substituted heterocyclic group, hydroxy lower alkyl,
hydroxy lower alkylamino lower alkyl, lower alkoxy lower alkyl,
carbamoyl lower alkyl, carboxy lower alkyl, lower
alkylcarbonylamino lower alkyl, lower alkoxycarbonylamino lower
alkyl, lower alkyloxy, the other various optionally substituted
lower alkyl, lower alkyl having 2 kinds of substituents, or
optionally substituted heterocyclic group.)
13. A compound according to claim 1, ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate thereof,
wherein Z.sup.+ is a heterocyclic group of any one of the formulae:
267(wherein, R is independently hydrogen, lower alkyl, amino lower
alkyl, lower alkylamino lower alkyl, amino substituted with
optionally substituted heterocyclic group, or optionally
substituted heterocyclic group; R' is amino.)
14. A compound according to claim 1, ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate thereof,
wherein Z.sup.+ is a heterocyclic group of any one of the formulae:
268(wherein, Me is methyl.)
15. A compound according to claim 1, ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate thereof,
wherein T is S; X is halogen; A is a divalent group shown in any of
claims 5 to 9; Z.sup.+ is a heterocyclic group shown in any of
claims 1 to 14.
16. A compound according to claim 1, ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate thereof,
wherein T is S; X is halogen; A is a divalent group shown in claim
8; Z.sup.+ is a heterocyclic group shown in claim 12.
17. A compound according to claim 1, ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate thereof,
wherein T is S; X is halogen; A is a divalent group shown in claim
9; Z.sup.+ is a heterocyclic group shown in claim 13 or 14.
18. A compound according to claim 1, of the following formula, or
pharmaceutically acceptable salt or solvate thereof. 269(wherein, X
is halogen; Z.sup.+ is a heterocyclic group of any of the formulae)
270(wherein, Me is methyl)
19. A compound of the formula: 271(wherein, T is S, SO or O; X is
halogen, CN, carbamoyl optionally substituted with lower alkyl,
lower alkyl, lower alkoxy, or lower alkylthio; A is optionally
substituted lower alkylene (excluding that the substituent is
optionally substituted mono lower alkyl, optionally substituted
lower alkylidene, or optionally substituted lower alkylene);
Z.sup.+ is optionally substituted, a cation- and an N
atom-containing heterocyclic group), ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate thereof,
excluding that T is S; X is halogen and 1) A is methylene; Z.sup.+
is pyridinium or 2) 0 is dimethylmethylene; Z+is
imidazo[12-a]pyridinium).
20. A compound of claim 19, ester, amino-protected compound wherein
the amino bonds to a thiazole ring at the 7-position, or
pharmaceutically acceptable salt or solvate thereof, wherein T is
S, X is halogen or lower alkyl; A is methylene optionally
substituted with di-lower alkyl.
21. A compound of claim 20, ester, amino-protected compound wherein
the amino bonds to a thiazole ring at the 7-position, or
pharmaceutically acceptable salt or solvate thereof, of any of the
formula: 272273
22. A pharmaceutical composition containing a compound of claim 1,
ester, amino-protected compound wherein the amino bonds to a
thiazole ring at the 7-position, or pharmaceutically acceptable
salt or solvate thereof.
23. An antibacterial composition containing a compound of claim 1,
ester, amino-protected compound wherein the amino bonds to a
thiazole ring at the 7-position, or pharmaceutically acceptable
salt or solvate.
24. A compound or pharmaceutically acceptable salt, of the formula:
274(wherein, X is halogen, CN, carbamoyl optionally substituted
with lower alkyl, lower alkyl, lower alkoxy, or lower alkylthio; A
is of the formula: 275R.sup.5 is hydrogen or carboxy-protecting
group; R.sup.6 is hydrogen or amino-protecting group R.sup.7 is
hydrogen or carboxy-protecting group)
25. A compound or pharmaceutically acceptable salt according to
claim 24, wherein X is halogen or lower alkyl.
26. A compound or pharmaceutically acceptable salt according to
herein X is halogen.
Description
TECHNICAL FIELD
[0001] The present invention relates to cephem compounds having a
broad antibacterial spectrum over various pathogenic bacteria and
pharmaceutical compositions containing the same, as well as a
production method and intermediates therefor. The compounds of the
present invention are stable against .beta.-lactamase and
efficacious against .beta.-lactamase-producing cephem-resistant
bacteria including Pseudomonas aeruginosa.
BACKGROUND
[0002] Study of so-called broad spectrum cephem compounds having
potent antibacterial activities against various Gram-positive and
Gram-negative bacteria has recently been focused on cephem
compounds wherein the 7-side chain is substituted with
aminothiazole or aminothiadiazole and the 3-position with a
cyclic-type quarternary ammoniummethyl group. For example, the
known 7-aminothiazole types include cefepime hydrochloride (U.S.
Pat. No. 4,406,899), cefpirome sulfate (U.S. Pat. No. 4,609,653,
JP(A) S57-192394), and cefoselis sulfate (JP(A) H07-196665,
WO97/41128), and the 7-aminothiadiazole types include cefclidin
(U.S. Pat. No. 4,748,171), and cefozopran hydrochloride (U.S. Pat.
No. 4,864,022, JP(A) S62-149682, JP(A) H03-47189). Such types of
cephem compounds are also reported in JP Patent publication (Kokai)
S-58-4789 which discloses compounds having an "optionally
substituted 2 or more of N atoms--containing heterocycle cation
group" at the 3-position and in JP Patent publication (Kokai)
S-60-155183 which discloses compounds having a "2 or more of N
atoms--containing unsaturated condensed heterocyclic cation group"
at the 3-position.
[0003] Documents such as JP Patent publication (Kokai) S-60-97982,
JP Patent publication (Kokai) S-59-130294, JP Patent publication
(Kokai) S-60-34973, JP Patent publication (Kokai) S-62-114990, JP
Patent publication (Kokai) S-64-42491, and WO87/06232 etc. disclose
cephem compounds which have a halogen on an aminothiazole ring at
the 7-position or which are substituted with COOH at the end of the
oxime part on the 7-side chain. These documents do not disclose a
cephem compound having the both structural characteristics.
[0004] A cephem compound, which has a halogen on an aminothiazole
ring at the 7-position and is substituted with COOH at the end of
the oxime part on the 7-side chain, is known in JP Patent
publication (Kokai) S-60-231684. However, a specifically disclosed
compound is that wherein the methylene group bonding to the oxime
part on the 7-side chain is non-substituted or dimethyl-substituted
type. JP Patent publication (Kokai) S-57-131794 and JP Patent
publication (Kokai) H-1-308286 discloses compounds wherein the
methylene group bonding to the oxime part on the 7-side chain is
substituted with monomethyl, however, the configuration is not
specified and a quarternary ammonium group is not disclosed as a
possible substituent on the methylene group at the 3-position.
Further, any antibacterial activities against cephem-resistant
Pseudomonas aeruginosa are not discribed therein.
[0005] A cephem compound having a quarternary ammonium group at the
3-position and a side chain of aminothiazole/oxime type at the
7-position, so-called broad spectrum antibacterial-type cephem, is
known as being efficatious against G(-) bacteria including
Pseudomonas aeruginosa. For example, ceftazidime has been reported
as being stable against .beta.-lactamase and possesing a relatively
potent activity against .beta.-lactamase-producing Pseudomonas
aeruginosa(Acta Microbiologica Hungarica 35 (4), pp. 327-359
(1988)).
[0006] Under the above circumstances, among G(-) bacteria, the
number of bacteria resistant to some broad spectrum
antibacterial-type cephems has recently increased. The frequency of
clinical isolation of cephem-resistant Pseudomonas aeruginosa,
which highly produce .beta.-lactamase, esp. Class C-type
.beta.-lactamase, has raised, which is recognized as a social
problem worldwide ("Classification and Epidemiology of Recent
.beta.-lactamase", Clinic and Microorganism Vol.26 No.2 1999.3 P
103-109). However, a cephem compound with a potent activity against
such cephem-resistant Pseudomonas aeruginosa has not been
reported.
[0007] Therefore, the development of a novel cephem compound with
broad antibacterial spectrum, preferably a compound possessing a
potent activity against cephem-resistant Pseudomonas aeruginosa
which produce .beta.-lactamase has been desired. In preference,
such a compound is useful as an injection.
DISCLOSURE OF THE INVENTION
[0008] The present inventors have found that the stability of a
cephem compound against .beta.-lactamase produced by
cephem-resistant Pseudomonas aeruginosa can be improved so as to
enhanse the antibacterial activity against such Pseudomonas
aeruginosa, by means of introducing a halogen atom or the like into
an aminothiazole ring on the 7-side chain, a carboxyl group into
the end of the oxime group bonding to the carbon atom at
.alpha.-position, and an N-containing heterocyclic group,
preferably a quarternary ammonium group into the 3-position,
respectively.
[0009] As a more preferable embodiment, the inventors have found
that the antibacterial activity can further be enhansed by
introducing a lower alkyl, preferably methyl as
.alpha.-configuration into the methylene group, whereby to
accomplish the present invention shown below.
[0010] 1. A compound of the formula 2
[0011] (wherein,
[0012] T is S, SO or O;
[0013] X is halogen, CN, carbamoyl optionally substituted with
lower alkyl, lower alkyl, lower alkoxy, or lower alkylthio;
[0014] A is substituted lower alkylene (wherein the substituent is
optionally substituted mono lower alkyl, optionally substituted
lower alkylidene, or optionally substituted lower alkylene)
[0015] Z.sup.+ is an optionally substituted, a cation and an N
atom-containing heterocyclic group), ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate
thereof.
[0016] 2. A compound according to the above 1 wherein T is S,
ester, amino-protected compound wherein the amino bonds to a
thiazole ring at the 7-position, or pharmaceutically acceptable
salt or solvate thereof.
[0017] 3. A compound according to the above 1 wherein T is O,
ester, amino-protected compound wherein the amino bonds to a
thiazole ring at the 7-position, or pharmaceutically acceptable
salt or solvate thereof.
[0018] 4. A compound according to the above 1 wherein X is halogen
or lower alkyl, ester, amino-protected compound wherein the amino
bonds to a thiazole ring at the 7-position, or pharmaceutically
acceptable salt or solvate thereof.
[0019] 5. A compound according to the above 1 wherein A is of the
formula: 3
[0020] (wherein, R.sup.1 and R.sup.2 are different each other and
independently hydrogen or optionally substituted lower alkyl, or
taken together may form optionally substituted lower alkylidene or
optionally substituted lower alkylene.), ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate
thereof.
[0021] 6. A compound according to the above 5 wherein A is a
divalent group of any of the following formulae, ester,
amino-protected compound wherein the amino bonds to a thiazole ring
at the 7-position, or pharmaceutically acceptable salt or solvate
thereof. 4
[0022] (wherein, Me is methyl; Et is ethyl; i-Pr is isopropyl)
[0023] 7. A compound according to the above 5 wherein R.sup.1 and
R.sup.2 are different each other and independently hydrogen or
lower alkyl, ester, amino-protected compound wherein the amino
bonds to a thiazole ring at the 7-position, or pharmaceutically
acceptable salt or solvate thereof.
[0024] 8. A compound according to the above 5 wherein R.sup.1 and
R.sup.2 are different each other and independently hydrogen or
methyl, ester, amino-protected compound wherein the amino bonds to
a thiazole ring at the 7-position, or pharmaceutically acceptable
salt or solvate thereof.
[0025] 9. A compound according to the above 5 wherein "-A--COOH" is
a group of the formula: 5
[0026] ester, amino-protected compound wherein the amino bonds to a
thiazole ring at the 7-position, or pharmaceutically acceptable
salt or solvate thereof.
[0027] 10. A compound according to the above 1 wherein Z.sup.+ is a
saturated or unsaturated, monocyclic or condensed cyclic, and at
least one or more of N atoms-containing quarternary ammonium group
of the formula: 6
[0028] which may have 1 to 4 substituents, ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate
thereof.
[0029] 11. A compound according to the above 1, ester,
amino-protected compound wherein the amino bonds to a thiazole ring
at the 7-position, or pharmaceutically acceptable salt or solvate
thereof, wherein Z.sup.+ is a heterocyclic group of any one of the
formulae: 78
[0030] (wherein, R.sup.3 and R.sup.4 each is independently
hydrogen, optionally substituted lower alkyl, optionally
substituted cycloalkyl, optionally substituted lower alkenyl,
optionally substituted amino, hydroxy, halogen, optionally
substituted carbamoyl, optionally substituted alkyloxy, or
optionally substituted heterocyclic group.)
[0031] 12. A compound according to the above 1, ester,
amino-protected compound wherein the amino bonds to a thiazole ring
at the 7-position, or pharmaceutically acceptable salt or solvate
thereof, wherein Z.sup.+ is a heterocyclic group of any one of the
formulae: 9
[0032] (wherein, R and R' each is independently hydrogen, lower
alkyl, amino, mono- or di- lower alkylamino, lower alkenyl, amino
lower alkyl, lower alkylamino lower alkyl, lower alkylamino lower
alkylamino, amino lower alkyloxyamino, amino substitute with
optionally substituted heterocyclic group, hydroxy lower alkyl,
hydroxy lower alkylamino lower alkyl, lower alkoxy lower alkyl,
carbamoyl lower alkyl, carboxy lower alkyl, lower
alkylcarbonylamino lower alkyl, lower alkoxycarbonylamino lower
alkyl, lower alkyloxy, the other various optionally substituted
lower alkyl, lower alkyl having 2 kinds of substituents, or
optionally substituted heterocyclic group.)
[0033] 13. A compound according to the above 1, ester,
amino-protected compound wherein the amino bonds to a thiazole ring
at the 7-position, or pharmaceutically acceptable salt or solvate
thereof, wherein Z.sup.+ is a heterocyclic group of any one of the
formulae: 10
[0034] (wherein, R is independently hydrogen, lower alkyl, amino
lower alkyl, lower alkylamino lower alkyl, amino substituted with
optionally substituted heterocyclic group, or optionally
substituted heterocyclic group; R' is amino.)
[0035] 14. A compound according to the above 1, ester,
amino-protected compound wherein the amino bonds to a thiazole ring
at the 7-position, or pharmaceutically acceptable salt or solvate
thereof, wherein Z.sup.+ is a heterocyclic group of any one of the
formulae: 11
[0036] (wherein, Me is methyl.)
[0037] 15. A compound according to the above 1, ester,
amino-protected compound wherein the amino bonds to a thiazole ring
at the 7-position, or pharmaceutically acceptable salt or solvate
thereof, wherein T is S; X is halogen; A is a divalent group shown
in any of the above 5 to 9; Z.sup.+ is a heterocyclic group shown
in any of the above 10 to 14.
[0038] 16. A compound according to the above 1, ester,
amino-protected compound wherein the amino bonds to a thiazole ring
at the 7-position, or pharmaceutically acceptable salt or solvate
thereof, wherein T is S; X is halogen; A is a divalent group shown
in the above 8; Z.sup.+ is a heterocyclic group shown in the above
12.
[0039] 17. A compound according to the above 1, ester,
amino-protected compound wherein the amino bonds to a thiazole ring
at the 7-position, or pharmaceutically acceptable salt or solvate
thereof, wherein T is S; X is halogen; A is a divalent group shown
in the above 9; Z.sup.+ is a heterocyclic group shown in the above
13 or 14.
[0040] 18. A compound according to the above 1 of the following
formula, or pharmaceutically acceptable salt or solvate thereof.
12
[0041] (wherein, X is halogen; Z.sup.+ is a heterocyclic group of
any of the formulae) 13
[0042] (wherein, Me is methyl)
[0043] 19. A compound of the formula: 14
[0044] (wherein,
[0045] T is S, SO or O;
[0046] X is halogen, CN, carbamoyl optionally substituted with
lower alkyl, lower alkyl, lower alkoxy, or lower alkylthio
[0047] A is optionally substituted lower alkylene (excluding that
the substituent is optionally substituted mono lower alkyl,
optionally substituted lower alkylidene, or optionally substituted
lower alkylene);
[0048] Z.sup.+ is optionally substituted, a cation- and an N
atom-containing heterocyclic group), ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate thereof,
excluding that T is S; X is halogen and 1) A is methylene; Z.sup.+
is pyridinium or 2) A is dimethylmethylene; Z.sup.+ is
imidazo[1,2-a]pyridinium).
[0049] 20. A compound of the above 19, ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate thereof,
wherein T is S, X is halogen or lower alkyl; A is methylene
optionally substituted with di-lower alkyl.
[0050] 21. A compound of the above 20, ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate thereof,
of any of the formula: 15
[0051] 22. A pharmaceutical composition containing a compound of
the above 1 to 21, ester, amino-protected compound wherein the
amino bonds to a thiazole ring at the 7-position, or
pharmaceutically acceptable salt or solvate thereof.
[0052] 23. An antibacterial composition containing a compound of
the above 1 to 21, ester, amino-protected compound wherein the
amino bonds to a thiazole ring at the 7-position, or
pharmaceutically acceptable salt or solvate.
[0053] 24. A compound or pharmaceutically acceptable salt, of the
formula: 16
[0054] (wherein, X is halogen, CN, carbamoyl optionally substituted
with lower alkyl, lower alkyl, lower alkoxy, or lower alkylthio; A
is of the formula: 17
[0055] R.sup.5 is hydrogen or carboxy-protecting group; R.sup.6 is
hydrogen or amino-protecting group; R.sup.7 is hydrogen or
carboxy-protecting group)
[0056] 25. A compound or pharmaceutically acceptable salt according
to the above 24, wherein X is halogen or lower alkyl.
[0057] 26. A compound or pharmaceutically acceptable salt according
to the above 24, wherein X is halogen.
[0058] Further, the present invention provides a method for
preparing the invention compounds and intermediates thereof, as
well as a method for prevention or treatment of bacterial infection
by administering the invention compound, and use of the invention
compound for preparing an antibacterial agent.
BEST MODE FOR CARRYING OUT THE INVENTION
[0059] Terms used herein are explained below. Unless otherwise
mentioned, each term, by itself or as part of another, has the
following meaning.
[0060] (Definition of T)
[0061] T is S, SO or O, preferably S or O, and more preferably
S.
[0062] (Definition of X)
[0063] X is halogen, CN, carbamoyl optionally substituted with
lower alkyl, lower alkyl, lower alkoxy, or lower alkylthio.
[0064] Halogen includes F, Cl, and Br, preferably Cl or Br, and
more preferably Cl.
[0065] Examples of lower alkyl include a straight or branched C1 to
C6 alkyl such as methyl, ethyl, n-propyl, i-propyl, t-butyl,
n-pentyl, and n-hexyl, and preferably is C1 to C3 alkyl, and more
preferably is methyl.
[0066] Examples of lower alkoxy include oxy bonding to lower alkyl,
such as methoxy, ethoxy, n-propoxy, i-propoxy, t-butoxy,
n-pentyloxy, and n-hexyloxy, preferably C1 to C3 alkoxy, and more
preferably methoxy.
[0067] Examples of lower alkylthio include thio bonding to the
lower alkyl, such as methylthio, ethylthio, n-propoxy,
i-propylthio, t-butylthio, n-pentylthio, and n-hexylthio,
preferably C1 to C3 alkylthio, and more preferably methylthio.
[0068] X is preferably halogen (e.g., Cl, Br) or lower alkyl (e.g.,
methyl), more preferably halogen.
[0069] (Definition of A)
[0070] A can be any of divalent groups which does not bring a
negative effect into the antibacterial activity of compound (I) or
compound (I-A), and preferably A is lower alkylene optionally
substituted with R.sup.1, R.sup.2 or the like. In compound (I), A
is substituted lower alkylene.
[0071] The lower alkylene is a divalent group derived from the
above-mentioned lower alkyl, preferably C1 to C3 alkylene, more
preferably methylene (--CH.sub.2--).
[0072] A is more preferably methylene substituted with the
following R.sup.1 and R.sup.2, and preferably A is of the following
configuration. 18
[0073] (Definition of R.sup.1, R.sup.2)
[0074] R.sup.1 and R.sup.2 are each independently hydrogen,
optionally substituted lower alkyl, or taken together may form
optionally substituted lower alkylidene or optionally substituted
lower alkylene, provided that in compound (I), R.sup.1 and R.sup.2
are different each other.
[0075] The lower alkyl includes the above-mentioned lower alkyl,
preferably C1 to C4 alkyl, more preferably methyl, ethyl, or propyl
(e.g., n-propyl, i-propyl), and most preferably methyl.
[0076] The lower alkylidene includes a divalent group which is
derived from the above lower alkyl by deducting two hydrogens
bonding to the same carbon atom, for example, .dbd.CH.sub.2,
.dbd.CHCH.sub.3, .dbd.CHCH.sub.2CH.sub.3, .dbd.C(CH.sub.3).sub.2,
.dbd.CHC(CH.sub.3).sub.3- , preferably .dbd.CH.sub.2,
.dbd.CHCH.sub.3, or .dbd.C(CH.sub.3).sub.2, and more preferably
.dbd.CH.sub.2.
[0077] The lower alkylene includes --(CH.sub.2) n--(n is an integer
from 2 to 4, preferably 2). R.sup.1 and R.sup.2 taken together may
form lower alkylene, which taken together with the neighboring
carbon atom can form the following cycloalkyl, preferably
cyclopropyl or cyclobutyl, and more preferably cyclopropyl. 19
[0078] When the above lower alkyl, lower alkylidene, or lower
alkylene is substituted, the substituents include halogen (e.g., F,
Cl), hydroxy, lower alkoxy (e.g., methoxy, ethoxy), and preferably
hydroxy.
[0079] The combination of (R.sup.1, R.sup.2 is preferably, (methyl,
hydrogen), (hydrogen, methyl), or (methyl, methyl) or taken
together may form .dbd.CH.sub.2, --(CH.sub.2).sub.2-- etc. In
compound (I), more preferred is hydrogen and lower alkyl, most
preferred is (R.sup.1, R.sup.2)=(methyl, hydrogen), or (hydrogen,
methyl). Particularly preferred is (hydrogen, methyl).
[0080] In compound (I), preferred are the following divalent
groups. 20
[0081] (wherein, Me is methyl; Et is ethyl; i-Pr is isopropyl.)
[0082] (Definition of Z.sup.+)
[0083] Z.sup.+ is an optionally substituted, a cation- and
N-containing heterocyclic group. Unless the pharmacological
activity is negatively influenced, the number and position of the
substituent, the kind of cation, and the kind of heterocycle can be
of variety. Z.sup.+ includes various kinds of groups which are well
known to or readily recognized by a skilled person in the invention
field as a heterocyclic group at the 3-position of cephem
compounds. The cation preferably locates around the N atom
neighboring to the 3-methylene of compound (I).
[0084] Z.sup.+ is preferably of the formula: 21
[0085] and a saturated or unsaturated, monocyclic or condensed
quarternary ammonium group which contains 1 or more, preferably 1
to 4, and more preferably 1 to 3 of N atoms, and optionally
substituted with 1 to 4, and preferably 1 to 2 substituents. The
heterocycle may further contain 1 or more of O and/or S.
[0086] The heterocycle is preferably a 5- to 10-, preferably 5- to
6-membered cycle.
[0087] The saturated N-containing heterocycle includes pyrrolidine,
pyrazolidine, thiazolidine, oxazolidine, imidazolidine, piperidine,
piperazine, morpholine, thiomorpholine, and a condensed ring
containing the same.
[0088] The unsaturated N-containing heterocycle includes a
monocycle (e.g.,: pyrrole, pyrazole, imidazole, oxazole,
isooxazole, thiazole, isothiazole, pyridine, pyridazine,
pyrimidine, pyrazine, triazine, triazole), and a condensed bicycle
containing the monocycle (e.g., indole, indolizine, benzimidazole,
benzpyrazole, indolizine, quinoline, isoquinoline, naphthylizine,
phthalazine, quinazoline, quinuclidine, benzoisooxazole,
benzpyrazole, benzoxazole, benzoxadiazole, benzisothiazole,
benzothiazole, benzotriazole, purine, indoline, pyrazoloimidazole,
pyridazineimidazole, thiazoloimidazole, tetrahydropyranopyridine,
oxazolo[4,5-c]pyridine, oxazolo[5,4-c]pyridine,
1H-pyrrolo[3,2-b]pyridine, 1H-pyrrolo[2,3-b]pyridine,
1H-pyrrolo[3,2-c]pyridine, 1H-pyrrolo[2,3-c]pyridine,
1H-pyrazolo[4,3-b]pyridine, 1H-pyrazolo[3,4-b]pyridine,
1H-imidazo[4,5-c]pyridine, 1H-imidazo[4,5-b]pyridine,
thiazolo[4,5-c]pyridine, thiazolo[5,4-b]pyridine,
1,4-dihydro-pyrido[3,4-- b]pyrazine,
1,3-dihydro-imidazo[4,5-c]pyridine, triazolopyridine).
[0089] In detail, Z.sup.+ includes optionally substituted
heterocyclic groups shown below. 2223
[0090] When the above heterocyclic group has a substituent(s), the
substituents include 1 or more, preferably 1 to 4, more preferably
1 to 3, and most preferably 1 to 2, same or different substituent
selected from the group consisting of lower alkyl (e.g., methyl,
ethyl, n-butyl), optionally substituted lower alkyl (substituent:
amino, lower alkylamino (e.g., --NHCH.sub.3), optionally
substituted lower alkylamino (e.g., --NHCH.sub.2CH.sub.2OH),
optionally substituted heterocyclic group (e.g., 2-pyrrolidinyl,
3-pyrrolidinyl, 5-(3-hydroxypyrrolidinyl)), hydroxy, cycloalkyl,
carboxy, lower alkoxy (e.g., methoxy), --OCOCH.sub.3,
--OCONH.sub.2, --OCONHOCH.sub.3, --OCONHOH, --OCONHCH.sub.3,
--OCON(CH.sub.3).sub.2, --OCONHN(CH.sub.3).sub.2, --ONHCOOCH.sub.3,
--CONH.sub.2, --CONHOCH.sub.3, --CONHOH, lower alkoxycarbonylamino
(e.g., --NHCOOCH.sub.3), lower alkylcarbonylamino (e.g.,
--NHCOCH.sub.3), --NHCONH.sub.2, --NHSO.sub.2NH.sub.2, --NHCHO,
--N(CH.sub.3)C.dbd.NH(NH.s- ub.2), halogen, oxo); optionally
substituted amino (substituent: lower alkyl (e.g., methyl, ethyl,
propyl), amino lower alkyl (e.g., --CH.sub.2CH.sub.2NH.sub.2,
--CH.sub.2CH(NH.sub.2)CH.sub.3,
--CH.sub.2CH.sub.2CH.sub.2NH.sub.2), lower alkylamino(lower)alkyl
(e.g., --CH.sub.2CH.sub.2NHCH.sub.3,
--CH.sub.2CH.sub.2CH.sub.2NHCH.sub.3), optionally substituted
heterocyclic group (e.g., 3-pyrrolidinyl, 4-piperidinyl,
2-thiazolyl, 5-(1-(2-hydroxyethyl)pyrazole),
5-(1-(2-aminoethyl)pyrazole)), lower alkyl substituted with an
optionally substituted heterocyclic group (e.g.,
(2-pyrrolidinyl)methyl, 2-(5-amino-1-(pyrazolyl)ethyl)), guanidino
lower alkyl (e.g., --CH.sub.2CH.sub.2NHC.dbd.NH(NH.sub.2)),
hydroxy(lower)alkyl (e.g., --CH.sub.2CH.sub.2OH,
--CH.sub.2CH.sub.2CH.sub.2OH), hydroxy(lower)alkylamino(lower)alkyl
(e.g., --CH.sub.2CH.sub.2NHCH.sub.2C- H.sub.2OH, amino(lower)
alkyloxy (e.g., --OCH.sub.2CH.sub.2NH.sub.2), lower
alkylamino(lower)alkyloxy (e.g., --OCH.sub.2CH.sub.2NHCH.sub.3,
--OCH.sub.2CH.sub.2CH.sub.2NHCH.sub.3), --CHO,
.dbd.CHN(CH.sub.3).sub.2, --NHCHO, optionally substituted carbamoyl
(e.g., --CONH.sub.2, --CONHCH.sub.2CH.sub.2NHCH.sub.3,
--CONHCH.sub.2CH.sub.2NHC.dbd.NH(NH.sub- .2)),
--COOCH.sub.2CH.sub.3, --CH.sub.2COOH, acyl (e.g., acetyl),
aminoacyl (e.g., --COCH.sub.2CH(CH.sub.3)NH.sub.2)); optionally
substituted carbamoyl (substituent:methyl, ethyl, --NHCHO); lower
alkylene (e.g., --CH.sub.2CH.sub.2--,
--CH.sub.2CH.sub.2CH.sub.2--); optionally substituted lower alkenyl
(e.g., --CH.sub.2CH.dbd.CH.sub.2); optionally substituted
cycloalkyl (e.g., cyclopropyl); hydroxy; nitro; cyano; aldehyde;
optionally substituted alkyloxy (e.g., --OCH.sub.3,
--OCH.sub.2CH.sub.3, --OCH.sub.2CH.sub.2NHCH.sub.3,
--OCH.sub.2CH.sub.2CH.sub.2NHCH.sub.3); lower alkylthio (e.g.,
--SCH.sub.3); lower alkoxycarbonyl (e.g., --COOCH.sub.2CH.sub.3);
halogen (e.g., F,Cl,Br), and optionally substituted heterocyclic
group.
[0091] The optionally substituted heterocyclic group includes the
above-mentioned Z and the bonding position is optional. Preferred
is an N-containing saturated 4- to 6-membered ring, for example,
azetidinyl (e.g., 3-azetidinyl), pyrrolidinyl(e.g.,
3-pyrrolidinyl), piperidinyl (e.g., 4-piperidinyl,
1-(4-aminopiperidinyl), piperadinyl (e.g., 1-piperadinyl,
1-(3-methylpiperadinyl), pyrrolyl (e.g., 3-pyrrolyl,4-(2-carbamoyl
pyrrolyl)), pyrazolyl (e.g., 1-pyrazolyl, 4-pyrazolyl), oxadiazolyl
(e.g., 2-oxadiazolyl), triazolyl (e.g., 1-triazolyl).
[0092] The above "lower" preferably means C1 to C6, and more
preferably C1 to C3. The substituents on the heterocyclic group
include preferably optionally substituted lower alkyl, optionally
substituted lower alkenyl, optionally substituted amino and
optionally substituted heterocyclic group, including the following
R.sup.3 and R.sup.4, "--R", and "--NHR".
[0093] Z.sup.+ is preferably the following heterocyclic group.
2425
[0094] Z.sup.+ is more preferably the following heterocyclic group,
and more preferably a group shown by b, d, e or n. 2627
[0095] R.sup.3 and R.sup.4 are each selected from the substituents
of the above-mentioned heterocycle, and preferred is hydrogen, the
above-mentioned optionally substituted lower alkyl, optionally
substituted lower alkenyl, optionally substituted amino or
optionally substituted heterocyclic group, including the following
"--R", "--R'", "--NHR", "--NHR'". R.sup.3 and R.sup.4 are each can
locate at any substitutable position.
[0096] Z.sup.+ is preferably the following heterocyclic group, and
more preferably b-1, b-2, d-1, d-3, or e-1. 2829
[0097] Each R and R' can be selected from the substituents of the
above-mentioned heterocycle, and preferred is independently
hydrogen, optionally substituted lower alkyl, optionally
substituted amino, or optionally substituted heterocyclic group.
More preferred is hydrogen, lower alkyl, lower alkenyl, amino lower
alkyl, aminohydroxy (lower)alkyl, lower alkylamino(lower)alkyl,
hydroxy(lower)alkyl, acyloxyamino(lower)alkyl,
acylamino(lower)alkyl, sulfonylamino(lower)alky- l,
carbamoyloxy(lower)alkyl, lower alkylhydrazonoxy(lower)alkyl,
carbamoylamino(lower)alkyl, alkoxycarbonylaminoxy(lower)alkyl,
lower alkoxy(lower) alkyl, carbamoyl(lower)alkyl, optionally
substituted cycloalkyl, lower alkyl substituted with an optionally
substituted heterocyclic group, carboxy(lower)alkyl, lower
alkoxycarbonylamino(lower)- alkyl, halogeno(lower)alkyl, lower
alkylamino, amino (lower)alkylamino, lower
alkylamino(lower)alkylamino,
hydroxy(lower)alkylamino(lower)alkylam- ino,
carbamoyloxy(lower)alkylamino, guanidino(lower)alkylamino,
optionally substituted carbamoyl, optionally substituted alkyloxy,
optionally substituted carbonylamino, amino substituted with an
optionally substituted heterocyclic group, amino(lower)alkyloxy, or
optionally substituted heterocyclic group.
[0098] R is preferably hydrogen, methyl, ethyl, cyclopropyl,
--CH.sub.2CH.sub.2NH.sub.2, --CH.sub.2CH.sub.2NHCH.sub.3,
--CH.sub.2CH.sub.2CH.sub.2NHCH.sub.3,
--CH.sub.2CH.sub.2NHCH.sub.2CH.sub.- 2OH,
--CH.sub.2CH.sub.2CH.sub.2NHCH.sub.2CH.sub.2OH,
--CH.sub.2CH.sub.2CH.sub.2NH.sub.2, --CH.sub.2CH(NH.sub.2)CH.sub.3,
--CH.sub.2CH.sub.2CH(NH.sub.2)CH.sub.3,
--CH.sub.2CH.sub.2CH(NH.sub.2)CH.- sub.2OH,
--CH.sub.2CH.sub.2CH(NH.sub.2)CH.sub.2OCOCH.sub.3,
--CH.sub.2CH(NHCH.sub.3)CH.sub.3, --CH.sub.2CH.sub.2OH,
--CH.sub.2CH.sub.2OCONH.sub.2, --CH.sub.2CH.sub.2OCONHOCH.sub.3,
--CH.sub.2CH.sub.2OCONHCH.sub.3,
--CH.sub.2CH.sub.2OCON(CH.sub.3).sub.2,
--CH.sub.2CH.sub.2OCONHN(CH.sub.3).sub.2,
--CH.sub.2CH.sub.2OCONHOH, --CH.sub.2CH.sub.2CH.sub.2OCONH.sub.2,
--CH.sub.2CH.sub.2ONHCOOCH.sub.3, --CH.sub.2CH.sub.2NHCOOH,
--CH.sub.2CONH.sub.2, --CH.sub.2CONHOCH.sub.3, --CH.sub.2CONHOH,
--CH.sub.2COOH, --CH.sub.2CH.sub.2NHCOCH.sub.3,
--CH.sub.2CH.sub.2NHCONH.sub.2,
--CH.sub.2CH.sub.2NHSO.sub.2NH.sub.2,
--CH.sub.2CH.sub.2NHCOOCH.sub.3,
--CH.sub.2CH.sub.2NHC(NH.sub.2).dbd.NH,
--CH.sub.2CH.sub.2CH.sub.2N(CH.sub.3)C(.sub.2).dbd.NH, NH.sub.2,
--NHCH.sub.2CH.sub.2NH.sub.2, --NHCH.sub.2CH.sub.2NHCH.sub.3,
--NH(CH.sub.3)CH.sub.2CH.sub.2NHCH.sub.3,
--N(CHO)CH.sub.2CH.sub.2NHCH.su- b.3,
--NHCOCH.sub.2CH(NH.sub.2)CH.sub.3,
--CONHCH.sub.2CH.sub.2NHCH.sub.3,
--CONHCH.sub.2CH.sub.2NHC(NH.sub.2).dbd.NH,
--OCH.sub.2CH.sub.2NHCH.sub.3- , 3-azethidinyl,
3-pyrrolidinylamino, 3-pyrrolidinyl, 1-pyrazolyl,
5-(1-(2-hydroxyethyl)pyrazolyl, 5-(1-(2-aminoethyl)pyrazolyl),
2-(1-(5-aminopyrazolyl))ethyl, 4-pyrazolyl, 3-pyrazolyl,
4-(2-carbamoylpyrolyl), 2-pyrrolidinylmethyl, 3-pyrrolidinylmethyl,
5-(3-hydroxypyrrolidinyl)methyl, 2-thiazolyl, 2-oxadiazolyl,
1-triazolyl, 1-(3-methylpiperadinyl), 1-(4-aminopiperidinyl), or
4-piperidinyl.
[0099] R' is preferably hydrogen or optionally substituted amino.
R' is preferably hydrogen, --NH.sub.2, --NHCH.sub.3,
--N(CH.sub.3).sub.2, --N.dbd.CHN(CH.sub.3).sub.2,
--N(CH.sub.3)CH.sub.2CH.sub.2NH.sub.2,
NHCH.sub.2CH.sub.2NHCH.sub.3, --NHCOOCH.sub.2CH.sub.3,
--NHOCH.sub.3, or --NHCH.sub.2COOH.
[0100] Z.sup.+ is more preferably the following group. 30
[0101] (wherein, each R is independently hydrogen, lower alkyl,
amino lower alkyl, lower alkylamino(lower)alkyl, amino substituted
with an optionally substituted heterocyclic group, or optionally
substituted heterocyclic group; R' is amino)
[0102] Z.sup.+ is most preferably the following group. 31
[0103] Compound (I) preferably includes the following
compounds.
[0104] (a) a compound wherein T is S; X is halogen or lower alkyl;
A is a divalent group shown in any of the above (5) to (9); Z.sup.+
is a heterocyclic group shown in any of the above-mentioned (10) to
(14).
[0105] (b) a compound wherein T is S; X is halogen or lower alkyl;
A is a divalent group shown in any of the above (8); Z.sup.+ is a
heterocyclic group shown in the above-mentioned (12). Preferably, X
is halogen and Z.sup.+ is the above-mentioned (b-1), (b-2), (d-1),
(d-3), (e-1), or (e-2).
[0106] (c) a compound wherein T is S; X is halogen; A is a divalent
group shown in the above
[0107] (9); Z.sup.+ is a heterocyclic group shown in the
above-mentioned (13) or (14).
[0108] Preferred embodiments include compounds of Examples 1, 3, 4,
5, 8, 9, 18, 19, 20, 79, 98, 111, 112, 124, 128, 132, 161, 164, and
185, and more preferred are compounds of Examples 8, 9, 18, 20, 79,
98, 124, 128, 132, 161, and 164.
[0109] The representative method for preparing compound (I) is
explained below. 32
[0110] (wherein, T is the same as defined above; R.sup.5 is
hydrogen or carboxy-protecting group R.sup.6 is hydrogen or
amino-protecting group; R.sup.7 is hydrogen or carboxy-protecting
group; R.sup.8 is hydrogen or amino-protecting group; R.sup.a is
hydrogen or carboxy-protecting group; Y is a leaving group (e.g.,
hydroxy, halogen (e.g., Cl, Br, I), carbamoyloxy, substituted
carbamoyloxy, acyloxy, methanesulfonyloxy, toluenesulfonyloxy);
Q.sup.- is a counter ion such as halogen).
[0111] (1) Production Method of Compound (IV), Material of 7-Side
Chain
[0112] (Method A)
[0113] Compound (II) and compound (III) are reacted to give
compound (IV). In this case, preferably R.sup.5 is hydrogen;
R.sup.6 is amino-protecting group; R.sup.7 is carboxy-protecting
group.
[0114] The amount of compound (III) is usually about 1 to 10 mol,
preferably about 1 to 2 mol per compound (II) 1 mol.
[0115] Examples of reaction solvent include ether (e.g., dioxane,
tetrahydrofran, diethylether, tert-butyl methyl ether,
diisopropylether), ester (e.g., ethyl formate, ethyl acetate,
n-butyl acetate), halogenated hydrocarbon (e.g., dichloromethane,
chloroform, carbon tetrachloride), hydrocarbon (e.g., n-hexane,
benzene, toluene), alcohol (e.g., methanol, ethanol, isopropanol),
amide (e.g., formamide, N,N-dimethylformamide, N,
N-dimethylacetamide, N-methylpyrrolidone), ketone (e.g., acetone,
methyl ethyl ketone), nitrile (e.g., MeCN, propionitrile), dimethyl
sulfoxide, water. These solvents can be used as single or a
mixture.
[0116] The reaction temperature is usually about -20 to 100.degree.
C., preferably about 0 to 5.degree. C.
[0117] (Method B)
[0118] Compound (V) is halogenated, optionally followed by
deprotection, to give compound (IV). In this case, preferably
R.sup.5 is a carboxy-protecting group in compound (V) and hydrogen
in compound (IV); R.sup.6 is an amino-protecting group; R.sup.7 is
a carboxy-protecting group.
[0119] Examples of halogenating agent include N-chlorosuccinimide,
N-chlorophthalimide, Cl.sub.2, N-bromosuccinimide,
N-bromophthalimide, Br.sub.2, and F.sub.2.
[0120] The amount of halogenating agent is usually about 1 to 20
mol, preferably about 1 to 2 mol per compound (V) 1 mol.
[0121] Examples of reaction solvent are the same as mentioned
above.
[0122] The reaction temperature is usually about -10 to 100.degree.
C., preferably about 0 to 50.degree. C.
[0123] (2) Acylation at 7-Position and 3-Side Chain Formation;
Production of Compound (VII) and (VIII)
[0124] 1) Acylation at 7-Position
[0125] Compound (VI) and compound (W) are reacted to give compound
(VII). Preferably, R.sup.a is a carboxy-protecting group; R.sup.5
is hydrogen; R.sup.6 is an amino-protecting group; R.sup.7 is a
carboxy-protecting group; R.sup.8 is hydrogen.
[0126] The amount of compound (IV) is usually about 1 to 5 mol,
preferably about 1 to 2 mol per compound (VI) 1 mol.
[0127] Examples of solvents used in the reaction include ethers
(e.g., dioxane, THF, diethylether, tert-butylmethylether, and
diisopropylether), esters (e.g., ethyl formate, ethyl acetate, and
n-butyl acetate), halogenated hydrocarbons (e.g., dichloromethane,
chloroform, and carbon tetrachloride), hydrocarbons (e.g.,
n-hexane, benzene, and toluene), amides (e.g., formamide,
N,N-dimethylformamide (DMF), N,N-dimethylacetoamide, and
N-methylpyrrolidone), ketones (e.g., acetone and
methylethylketone), nitriles (e.g., MeCN and propionitriles),
dimethylsulfoxide, and water.
[0128] The reaction temperature is usually about -40 to 100.degree.
C., preferably about 0 to 30.degree. C. Compound (VI, VII, VIII,
T=SO) can be prepared by oxidating compound (VI, VII, VIII, T=S).
Preferably, compound (VII, T=SO) can be prepared by oxidating
compound (VII, T=S).
[0129] Examples of oxidating agent include m-chloroperoxybenzoic
acid (m-CPBA), hydrogen peroxid, and peracetic acid.
[0130] Compound (VI) can be prepared according to the method
described in JP Patent publication (Kokai) S-60-231684, JP Patent
publication (Kokai) S-62-149682 or the like.
[0131] The above amidation can be conducted after convertion of the
carboxyl moiety into a reactive derivative. Examples of the
reactive derivative include inorganic base salts, organic base
salts, acid halides, acid azides, acid anhydrides, mixed acid
anhydride, active amide, active ester, active thioester. The
inorganic base includes alkaline metals (e.g., Na and K) and
alkaline earth metals (e.g., Ca and Mg); The organic base includes
trimethylamine, triethylamine, tert-butyldimethylamine,
dibenzylmethylamine and benzyldimethylamine; the acid halide
includes acid chloride and acid bromide; the mixed acid anhydride
includes mixed monoalkylcarboxylic acid anhydride, mixed aliphatic
carboxylic acid anhydride, aromatic carboxylic acid anhydride,
oraganic sulfonic acid anhydride, the active amide includes amide
formed with heterocyclic compound containing N atom, for example.
Examples of the active ester include organic phosphate esters
(e.g., diethoxy phosphate ester and diphenoxy phosphate ester),
p-nitrophenyl ester, 2,4-dinitrophenyl ester, cyanomethyl ester,
and the active thioester includes esters formed with aromatic
heterocyclicthio compound (e.g., 2-pyridylthio ester).
[0132] The above reaction may be carried out using an appropriate
condensing agent, if necessary. Examples of the condensing agent
include e.g.,
1-dimethylaminopropyl-3-ethylcarbodiimide.multidot.hydrochloride
(WSCD.multidot.HCl), N,N'-dicyclohexylcarbodiimide,
N,N'-carbonyldiimidazole, N,N'-thiocarbonyldiimidazole,
N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline, phosphorus
oxychloride, alkoxyacetylene, 2-chloropyridiniummethyl iodine, and
2-fluoropyridiniummethyl iodine, trifluoroacetic acid
anhydride.
[0133] 2) 3-Side Chain Formation
[0134] Compound (VII) and Z (optionally substituted N-containing
heterocycle) is reacted to give compound (VIII). Preferably,
R.sup.6 is an amino-protecting group; R.sup.7 is a
carboxy-protecting group; R.sup.a is a carboxy-protecting group.
Compound (VIII) may have a functional group as a substituent on Z,
which can be protected.
[0135] The amount of Z is usually about 1 to 10 mol, preferably
about 1 to 2 mol per compound (VII) 1 mol.
[0136] Examples of solvents include ethers (e.g., dioxane, THF,
diethyl ether, tert-butyl methyl ether, and diisopropyl ether),
esters (e.g., ethyl formate, ethyl acetate, and n-butyl acetate),
halogenated hydrocarbons (e.g., dichloromethane, chloroform, and
carbon tetrachloride), hydrocarbons (e.g., n-hexane, benzene, and
toluene), amides (e.g., formamide, N,N-dimethylformamide (DMF),
N,N-dimethylacetoamide, and N-methylpyrrolidone), ketones (e.g.,
acetone and methyl ethyl ketone), nitriles (e.g., MeCN and
propionitrile), dimethyl sulfoxide, and water.
[0137] The reaction temperature is usually about 0 to 100.degree.
C., preferably about 0 to 50.degree. C., and more preferably about
10 to 30.degree. C.
[0138] Examples of reaction-accelerating agent include NaI.
[0139] Compound (VIII, T=S) can be prepared by reducing compound
(VIII,T=SO). The reducing agent includes metals (e.g., Zn, Sn) and
iodide (e.g., KI).
[0140] (3) 3-Side Chain Formation and Acylation at 7-Position;
Production of Compound (IX) and (VIII)
[0141] 1) 3-Side Chain Formation
[0142] Compound (VI) and Z (optionally substituted N-containing
heterocycle) are reacted to give compound (IX). Preferably, R.sup.8
is hydrogen; R.sup.a is a carboxy-protecting group. Compound (VIII)
may have a functional group as a substituent on Z, which can be
protected.
[0143] The amount of Z is usually about 1 to 10 mol, preferably
about 1 to 2 mol per compound (VI) 1 mol.
[0144] Examples of solvents include ethers (e.g., dioxane, THF,
diethyl ether, tert-butyl methyl ether, and diisopropyl ether),
esters (e.g., ethyl formate, ethyl acetate, and n-butyl acetate),
halogenated hydrocarbons (e.g., dichloromethane, chloroform, and
carbon tetrachloride), hydrocarbons (e.g., n-hexane, benzene, and
toluene), amides (e.g., formamide, N,N-dimethylformamide (DMF),
N,N-dimethylacetoamide, and N-methylpyrrolidone), ketones (e.g.,
acetone and methyl ethyl ketone), nitriles (e.g., MeCN and
propionitrile), dimethyl sulfoxide, and water.
[0145] The reaction temperature is usually about 0 to 100.degree.
C., preferably about 0 to 50.degree. C., and more preferably about
10 to 30.degree. C.
[0146] Examples of reaction-accelerating agent include NaI.
[0147] Compound (IX, T=SO) can be prepared by oxidating compound
(IX, T=S).
[0148] Examples of oxidating agent include m-chloroperoxybenzoic
acid (m-CPBA), hydrogen peroxid, and peracetic acid.
[0149] 2) Acylation at 7-Position
[0150] Compound (IX) and compound (I) are reacted to give compound
(VIII). Preferably, R.sup.a is a carboxy-protecting group; R.sup.5
is hydrogen; R.sup.6 is an amino-protecting group; R.sup.7 is a
carboxy-protecting group; R.sup.8 is hydrogen.
[0151] The amount of compound (IV) is usually about 1 to 5 mol,
preferably about 1 to 2 mol per compound (IX) 1 mol.
[0152] Examples of solvents include ethers (e.g., dioxane, THF,
diethyl ether, tert-butylmethyl ether, and diisopropyl ether),
esters (e.g., ethyl formate, ethyl acetate, and n-butyl acetate),
halogenated hydrocarbons (e.g., dichloromethane, chloroform, and
carbon tetrachloride), hydrocarbons (e.g., n-hexane, benzene, and
toluene), amides (e.g., formamide, N,N-dimethylformamide (DMF),
N,N-dimethylacetoamide, and N-methylpyrrolidone), ketones (e.g.,
acetone and methyl ethyl ketone), nitriles (e.g., MeCN and
propionitrile), dimethyl sulfoxide, and water.
[0153] The reaction temperature is usually about -40 to 100.degree.
C., preferably about 0 to 30.degree. C., and more preferably about
10 to 30.degree. C.
[0154] The above amidation can be conducted after convertion of the
carboxyl moiety into a reactive derivative or by using an
appropriate condensing agent. Examples of the reactive derivative
include inorganic base salts, organic base salts, acid halides,
acid azides, acid anhydrides, mixed acid anhydride, active amide,
active ester, active thioester.
[0155] (4) Deprotection
[0156] Compound (VIII) can be deprotected by a method well known to
a person skilled in the art to give compound (I).
[0157] Examples of solvents include ethers (e.g., dioxane, THF,
diethyl ether, tert-butylmethyl ether, and diisopropyl ether),
esters (e.g., ethyl formate, ethyl acetate, and n-butyl acetate),
halogenated hydrocarbons (e.g., dichloromethane, chloroform, and
carbon tetrachloride), hydrocarbons (e.g., n-hexane, benzene, and
toluene), amides (e.g., formamide, N,N-dimethylformamide (DMF),
N,N-dimethylacetoamide, and N-methylpyrrolidone), ketones (e.g.,
acetone, and methyl ethyl ketone), nitriles (e.g., MeCN and
propionitrile), dimethyl sulfoxide, and water.
[0158] The reaction temperature is usually about -30 to 100.degree.
C., preferably about 0 to 50.degree. C., and more preferably about
0 to 10.degree. C.
[0159] Examples of catalyst include Lewis acid (e.g., AlCl.sub.3,
SnCl.sub.4, TiCl.sub.4) and protonic acid (e.g., HCl,
H.sub.2SO.sub.4, HClO.sub.4, HCOOH, phenol).
[0160] Thus obtained compound (I) can further be chemically
modified to give the other compound (I), ester, amino-protected
compound wherein the amino bonds to a thiazole ring at the
7-position, or pharmaceutically acceptable salt or solvate
thereof.
[0161] Ester of compound (I) preferably includes esters which is
formed at carboxyl moiety on the 7-side chain or at the 4-position.
The ester compound formed at carboxyl moiety on the 7-side chain
means a compound having an ester structure of the formula: 33
[0162] (R.sup.7 is an ester residue such as carboxy-protecting
group)
[0163] The ester includes an ester which is readily metabolized in
the body to carboxy.
[0164] The ester compound formed at the carboxyl moiety at the
4-position means a compound having an ester structure of the
formula: 34
[0165] (R.sup.a is an ester residue such as carboxy-protecting
group; Q.sup.- is an counter ion such as halogen)
[0166] The ester includes an ester readily metabolized in the body
to carboxy.
[0167] Examples of the above carboxy-protecting group include lower
alkyl (e.g., methyl, ethyl, t-butyl), (substituted)aralkyl (e.g.,
benzyl, benzhydryl, p-methoxybenzyl, p-nitrobenzyl), silyl group
(e.g., t-butyldimethylsilyl, diphenyl t-butylsilyl).
[0168] The amino-protected compound (I) wherein the amino bonds to
a thiazole ring at the 7-position means a compound wherein the
thiazole ring is of the formula 35
[0169] (R.sup.6 is an amino-protecting group) The amino-protecting
group includes that which is readily metabolized in the body to
amino. The above amino-protecting group includes lower
alkoxycarbonyl (e.g., t-butoxycarbonyl, benzyloxycarbonyl,
p-nitrobenzyloxy carbonyl), (substituted) aralkanoyl (e.g.,
p-nitrobenzoyl), acyl (e.g., formyl, chloro acetyl).
[0170] Examples of the pharmaceutically acceptable salt of compound
(I) include salts formed with inorganic bases, ammonia, organic
bases, inorganic acids, organic acids, basic amino acids, halogen
ions or the like, and inner salts. Examples of the inorganic base
include alkali metal (e.g., Na and K) and alkaline earth metal
(e.g., Mg).
[0171] Examples of the organic base include procaine,
2-phenylethylbenzylamine, dibenzylethylenediamine, ethanolamine,
diethanolamine, tris(hydroxymethyl)aminomethane,
polyhydroxyalkylamine, and N-methyl glucosamine. Examples of the
inorganic acid include hydrochloric acid, hydrobromic acid,
sulfuric acid, nitric acid, and phosphoric acid. Examples of the
organic acid include p-toluene sulfonic acid, methanesulfonic acid,
formic acid, trifluoroacetc acid and maleic acid. Examples of the
basic amino acid include lysine, arginine, ornithine and histidine.
Examples of solvate of compound (1) include water and alcohol.
[0172] The present invention further provides the above-mentioned
compound (I-A). The definition of each group in compound (I-A) and
production method thereof are in accordance with those for the
above-mentioned compound (I).
[0173] Further, the present invention provides the above-mentioned
compound (IV), (VII) and (IX). These compounds are useful as
intermediates of compound (I). In particular, compound (IV) is an
important intermediate for the exhibition of antibacterial activity
of compound (I).
[0174] In compound (IV), X is preferably halogen or lower alkyl and
more preferably halogen (e.g., Cl, Br).
[0175] The invention compounds with a broad antibacterial spectrum
are useful for the prevention or treatment of various diseases
caused by enteropathogenic bacteria of mammals, including
respiratory tract infection, urinary tract infection, repiratory
tract infection, septicemia, nephritis, cholecystitis, oral
infection, endocarditis, pneumonia, bone meningitis, otitis media,
enteritis, empyema, wound infection, and opportunistic
infection.
[0176] The invention compound exhibits a potent antibacterial
activity, preferably against gram-negative bacteria including
Pseudomonas, E. coli, and Haemophilus influenzae. In particularly,
the compound is extremely stable against .beta.-lactamase, esp.,
C-class .beta.-lactamase, produced by cephem-resistant Pseudomonas,
thus being efficacious against the Pseudomonas. Accordingly, the
invention compound can bring an excellent clinical effect even by
single use without a .beta.-lactamase inhibitor. Further, the
invention compound possesses an antibacterial activity against
gram-positive bacteria including methicillin-resistant
Staphylococcus aureus (MRSA) and penicillin-resistant
Staphylococcus aureus (PRSE). Moreover, it has some excellent
characteristics in the pharmacokinetics, such as blood
concentration, continuous effect, and transition into tissues. In
another embodiment, the invention compound has a high water
solubility and particularly suitable for an injection agent.
[0177] Compound (I) or (I-A) can be administered parenterally or
orally as an agent of injection, capsule, tablet or granule.
Preferably, it can be administered as an injection agent. The daily
dose for a patient or animal is usually about 0.1 to 100 mg/kg,
preferably about 0.5 to 50 mg/kg, optionally in 2 to 4 divisions.
The pharmaceutically acceptable carriers used for injections
include e.g., distilled water, physiologic saline, and pH adjusting
agents such as bases. For preparing capsules, granules, and tables,
other pharmaceutically acceptable carriers can be used, such as
excipients (e.g., starch, lactose, sucrose, calcium carbonate,
calcium phosphate), binders (e.g., starch, Arabian gum,
carboxymethyl cellulose, hydroxypropyl cellulose, crystalline
cellulose), and lubricants (e.g., magnesium stearate, talc).
[0178] Reference Examples and Examples are shown below.
[0179] (Abbreviation)
[0180] Me: methyl; Et: ethyl; iPr: isopropyl; Bu: butyl; Ac:
acetyl; DMF: dimethylformamide; THF: tetrahydrofran; DMA:
dimethylacetoamide: WSCD 1-dimethylaminopropyl-3-ethylcarbodiimide;
m-CPBA: m-chloroperoxybenzoic acid; Boc: t-butoxycarbonyl; PMB:
p-methoxybenzyl; BH: benzhydryl; TBS: t-butyldimethylsilyl; Ph:
phenyl
REFERENCE EXAMPLE 1
Synthesis of 7-Side Chain
[0181] 36
[0182] (1) To a solution of compound 1 (71.4 g, 200 mmol) in dry
CH.sub.2Cl.sub.2 714 ml, was added at room temperature
4-dimethylaminopyridine (DMAP) 2.44 g (0.1 eq) and Boc.sub.2O 95.2
ml (2.1 eq) was added dropwise. The reaction mixture was stirred at
room temperature for 21 hr, which was poured to a saturated
NH.sub.4Cl aq. solution containing 1N--HCl 19 ml, then the organic
layer was separated, washed with brine, dried over anhydrous
Na.sub.2SO.sub.4, and concentrated in vacuum to give compound 2
(112 g).
[0183] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.35(3H, t, J=6.9 Hz),
1.43(9H, s), 1.51(6H, s), 1.53(18H, s), 4.36(2H, q, J=6.9 Hz),
7.38(1H, s).
[0184] IR (KBr) cm.sup.-1: 2979, 2938, 1781, 1743, 1722, 1494,
1457, 1369, 1346, 1328, 1284, 1135.
[0185] MS(ESI):558.sup.+(M+H.sup.+).
[0186] Elemental analysis C.sub.25H.sub.39N.sub.3O.sub.9S.
[0187] Calc.: C, 53.84; H, 7.05; N, 7.54; S, 5.75 (%). Found: C,
53.70; H, 6.91; N, 7.49; S, 5.81 (%).
[0188] (2) To a solution of compound 2 101 g (181 mmol) in DMF 400
ml, was added at room temperature N-chlorosuccinimide (NCS) 9.65 g
(0.4 eq) and the mixture was stirred at room temperature for 3 hr.
NCS 9.65 g (0.4 eq) was added thereto and the mixture was stirred
at room temperature for 2 hr, then NCS 9.65 g (0.4 eq) was further
added followed by 4 hr stirring at room temperature. The mixture
was allowed to stand at 4.degree. C. overnight, which was poured to
1000 ml water containing Na.sub.2SO.sub.4 30 g, followed by
extraction with AcOEt (500 ml.times.2). The obtained organic layer
was washed with brine, dried over anhydrous Na.sub.2SO.sub.4, and
concentrated in vacuum. Purification with silica gel column
chromatography, followed by concentration in vacuum, gave compound
3 (104 g).
[0189] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.34(3H, t, J=6.9 Hz),
1.44(9H, s), 1.52(6H, s), 1.53(18H, s), 4.33(2H, q, J=6.9 Hz).
[0190] IR (KBr) cm.sup.-1: 2979, 2938, 1781, 1743, 1722, 1494,
1457, 1369, 1346, 1328, 1284, 1135.
[0191] MS(ESI):614.sup.+(M+Na.sup.+).
[0192] Elemental analysis C.sub.25H.sub.38ClN.sub.3O.sub.9S.
[0193] Calc.: C, 50.71; H, 6.47; N, 7.10; S, 5.42; Cl, 5.99 (%).
Found: C, 50.57; H, 6.40; N, 7.01; S, 5.13; Cl, 5.93(%).
[0194] (3) To a solution of compound 3 83.2 g (140 mmol) in MeOH
1600 ml, 8N--NaOH 175 ml was added dropwise under ice-cooling. The
mixture was stirred under ice-cooling for 0.5 hr and further
stirred at room temperature for 5.5 hr. 5N--HCl 210 ml was added
dropwise (the pH of the reaction solution is 5.3) thereto and the
mixture was allowed to stand overnight at room temperature. The
mixture was concentrated under reduced pressure to remove MeOH,
resulting in precipitation of white precipitates, followed by
adding water 1000 ml and filtration. The obtained white solid was
washed with ice water and dried under reduced pressure to give
compound 4-1 60.9 g.
[0195] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.46(9H, s), 1.52(9H, s),
1.58(6H, s), 5.20-6.20(2H, brs).
[0196] IR (KBr) cm.sup.-1: 3426, 3220, 3081, 2981, 2937, 1720,
1556, 1455, 1394, 1369, 1249, 1155.
[0197] MS(ESI):464.sup.+(M+H.sup.+).
[0198] Elemental analysis
C.sub.18H.sub.26ClN.sub.3O.sub.7S.multidot.0.6H.- sub.2O.
[0199] Calc.: C, 45.54; H, 5.77; N, 8.85; S, 6.75; Cl, 7.47 (%).
Found: C, 45.38; H, 5.59; N, 8.82; S, 6.67; Cl, 7.75(%).
REFERENCE EXAMPLE 2
Synthesis of 7-Side Chain
[0200] 37
[0201] (1) To a solution of compound 5 (8.8 ml, 60 mmol) and
compound 6 (6.52 g 40 mmol) in dry CHCl.sub.3 180 ml, was added
dropwise triethylamine 6.12 ml under ice-cooling, and the mixture
was stirred at room temperature for 3 days. After adding
triethylamine 3.0 ml, the mixture was further stirred at room
temperature for 1 day, which was poured to a saturated NaHCO.sub.3
aq. solution, followed by extraction with CHCl.sub.3. The obtained
organic layer was washed with a saturated NH.sub.4Cl aq. solution,
dried over anhydrous MgSO.sub.4, and concentrated under reduced
pressure to give compound 7 (10.5 g).
[0202] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.49(9H, s), 4.71(2H, s),
7.70-7.90(4H, m).
[0203] IR (KBr) cm.sup.-1: 2980, 2939, 1788, 1745, 1730, 1465,
1441, 1374, 1247, 1186, 1160, 1137, 1043.
[0204] MS(ESI):300.sup.+(M+Na.sup.+).
[0205] Elemental analysis
C.sub.14H.sub.15NO.sub.5.multidot.0.2H.sub.2O.
[0206] Calc.: C, 59.87; H, 5.53; N, 4.99 (%). Found: C, 60.04; H,
5.55; N, 5.13 (%).
[0207] (2) To a solution of compound 7 (1.67 g 6 mmol) in dry
CH.sub.2Cl.sub.2 16 ml, was added methyl hydrazine 0.32 ml under
ice-cooling and the mixture was stirred for 15 min. The obtained
white precipitations were filtered off to give compound 8 in the
filtrate. MeOH 6 ml was added thereto under ice-cooling, and
compound 9 (1.53 g 5 mmol) was added thereto. After stirring under
ice-cooling for 10 min, the mixture was further stirred at room
temperature for 2.5 hr and under reflux for 1 hr, then allowed to
stand at room temperature for 3 days. The obtained precipitation
was filtered and washed with water to give compound 4-2 (1.36
g).
[0208] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.42(9H, s), 1.46(9H,
s), 4.36(2H, s), 6.0-9.0(1H, brs), 11.9(1H, brs).
[0209] IR (KBr) cm.sup.-1: 3429, 3136, 2982, 2936, 1739, 1715,
1626, 1557, 1458, 1392, 1381, 1370, 1249, 1157.
[0210] MS(FAB):434.sup.-(M-H.sup.-).
[0211] HR-MS(FAB): calcd for
C.sub.16H.sub.21Cl.sub.1N.sub.3O.sub.7S 434.0789 found
434.0782.
[0212] The relation of substituent, compound No and structure of
Example compounds are exemplified below.
1 I 38 Example of compound No 39 7-side chain 3-side chain X R1 R2
Z 1: H a: H H 1 40 R = 2: Me b: .dbd.CH.sub.2 2 41 a: H 3: Cl c:
--(CH.sub.2).sub.2-- 3 42 b: Me 4: Br d: Me Me 4 43 c:
(CH.sub.2).sub.2NHMe e: Me H 5 44 d: (CH.sub.2).sub.3NHMe f: H Me 6
45 g: Et H 7 46 h: H Et i: iPr H j: H iPr k: CH.sub.2OH H l: H
CH.sub.2OH
[0213] The structure of compound (I) of Examples 1 to 21 are shown
below.
2 (I) 47 Compound Example No X R1 R2 Z 1 I-2d-5d Me Me Me 5d 2
I-3a-5d Cl H H 5d 3 I-3d-1 Cl Me Me 1 4 I-3d-2a Cl Me Me 2a 5
I-3d-5d Cl Me Me 5d 6 I-3d-6d Cl Me Me 6d 7 I-3d-5c Cl Me Me 5c 8
I-3e-5d Cl Me H 5d 9 I-3f-5d Cl H Me 5d 10 I-3g-5d Cl Et H 5d 11
I-3h-5d Cl H Et 5d 12 I-3i-5d Cl iPr H 5d 13 I-3j-5d Cl H iPr 5d 14
I-3k-5d Cl CH.sub.2OH H 5d 15 I-3l-5d Cl H CH.sub.2OH 5d 16 I-3f-2a
Cl H Me 2a 17 I-3c-2a Cl --(CH.sub.2).sub.3-- 2a 18 I-3c-5d Cl
--(CH.sub.2).sub.3-- 5d 19 I-3b-5d Cl .dbd.CH.sub.2 5d 20 I-4d-5d
Br Me Me 5d 21 I-4f-5d Br H Me 5d
[0214] The synthesis method and physical data are shown below. The
synthesis was conducted according to the method of Example 2, 5
etc.
EXAMPLE 1
[0215] 48
[0216] I-2d-5d:
[0217] .sup.1H-NMR (D.sub.2O) .delta.: 1.46(6H, s), 2.27(3H, s),
2.31(2H, m), 2.69(3H, s), 3.06(2H, m), 3.18 and 3.39(2H, ABq,
J=17.7 Hz), 4.52(2H, t, J=7.2 Hz), 5.18(1H, d, J=4.8 Hz), 5.55 and
5.69(2H, ABq, J=15.0 Hz), 5.82(1H, d, J=4.8 Hz), 7.04(1H, d, J=3.6
Hz), 7.69(1H, dd, J=6.0 and 8.4 Hz), 8.12(1H, d, J=3.6 Hz),
8.59(1H, d, J=8.4 Hz), 8.65(1H, d, J=6.0 Hz).
[0218] IR (KBr) cm.sup.-1: 3413, 2983, 2458, 1774, 1610, 1498,
1467, 1392, 1359, 1288, 1195, 1162, 1122.
[0219] MS(ESI):671.sup.+(M+H.sup.+).
[0220] Elemental analysis
C.sub.29H.sub.34N.sub.8O.sub.7S.sub.2.multidot.5- .6H.sub.2O.
[0221] Calc.: C, 45.14; H, 5.90; N, 14.52; S, 8.31 (%). Found: C,
45.15; H, 5.32; N, 14.36; S, 8.49 (%).
[0222] Quaternary Salt Ester:
[0223] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37(9H, s), 1.38(6H,
s), 1.42(9H, s), 2.03(2H, m), 2.41(3H, s), 2.78(3H, brs), 3.18(2H,
m), 3.36 and 3.56(2H, m), 3.75(3H, s), 4.43(2H, m), 5.17(1H, d,
J=5.1 Hz), 5.21(2H, s), 5.22 and 5.29(2H, ABq, J=11.4 Hz), 5.67 and
5.72(2H, ABq, J=16.2 Hz), 5.96(1H, dd, J=5.1 and 8.7 Hz), 6.90(2H,
d, J=8.7 Hz), 6.96(1H, d, J=3.6 Hz), 7.33(2H, d, J=8.7 Hz),
7.34-7.45(5H, 7.78(5H, m), 7.78(1H, m), 8.43(1H, d, J=3.3 Hz),
8.62(1H, d, J=6.0 Hz), 8.88(1H, d, J=8.4 Hz), 9.49(1H, d, J=8.7
Hz), 12.1(1H, brs).
[0224] IR (KBr) cm.sup.-1: 3423, 3089, 2973, 2933, 1791, 1724,
1685, 1556, 1515, 1496, 1454, 1390, 1365, 1299, 1247, 1222, 1174,
1145, 1062, 1027.
[0225] MS(ESI):
1081.sup.+(C.sub.54H.sub.65N.sub.8O.sub.12S.sub.2.sup.+).
3-Chloromethyl Compound:
[0226] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.42(9H, s), 1.57(3H, s),
1.58(3H, s), 2.48(3H, s), 3.47 and 3.64(2H, ABq, J=18.3 Hz),
3.81(3H, s), 4.44 and 4.55(2H, ABq, J=11.7 Hz), 5.04(1H, d, J=5.1
Hz), 5.20 and 5.26(2H, ABq, J=12.0 Hz), 5.25(2H, s), 6.04(1H, dd,
J=5.1 and 9.3 Hz), 6.90(2H, d, J=9.0 Hz), 7.35(2H, d, J=9.0 Hz),
7.30-7.40(5H, m), 7.90(1H, d, J=9.3 Hz), 8.38(1H, brs).
[0227] IR (KBr) cm.sup.-1: 3386, 3283, 2979, 2937, 1789, 1726,
1692, 1613, 1557, 1515, 1455, 1383, 1367, 1300, 1247, 1224, 1142,
1094, 1061.
[0228] MS(ESI): 828.sup.+(M+H.sup.+).
[0229] Elemental analysis
C.sub.38H.sub.42ClN.sub.5O.sub.10S.sub.2.multido- t.0.05
CHCl.sub.3.multidot.0.7H.sub.2O.
[0230] Calc.: C, 53.96; H, 5.17; N, 8.27; S, 7.57; Cl, 4.81 (%).
Found: C, 54.03; H, 5.14; N, 8.16; S, 7.29; Cl, 4.81 (%).
[0231] 7-Side Chain
[0232] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39(9H, s), 1.41(6H,
s), 2.43(3H, s), 5.22(2H, s), 7.30-7.40(5H, m), 12.0(1H, brs).
[0233] IR (KBr) cm.sup.-1: 3430, 3193, 2981, 2937, 1731, 1614,
1596, 1562, 1455, 1392, 1369, 1299, 1228, 1187, 1141, 1062.
[0234] MS(ESI): 478.sup.+(M+H.sup.+).
EXAMPLE 2
[0235] 49
[0236] (1) A solution of compound 11-2 (1.20 g 1.53 mmol) in
CH.sub.2Cl.sub.2 12 ml was cooled to -50.degree. C. in nitrogen
atomosphere, to which was added 2 ml solution of 65% m-CPBA (366 mg
0.9 eq) and the mixture was stirred at -50.degree. C. to
-40.degree. C. for 15 min. The reaction mixture was poured to a
saturated Na.sub.2S.sub.2O.sub.3 solution and extracted with
CHCl.sub.3. The obtained organic layer was washed with a saturated
NaHCO.sub.3 aq. solution and brine, dried over anhydrous
MgSO.sub.4, and concentrated under reduced pressure. The obtained
compound 15 (1.18 g 1.47 mmol) was dissolved to DMF 2 ml under
nitrogen atomosphere, to which were added a solution of NaBr (303
mg 2 eq) and compound 13 (627 mg 1.55 eq) in DMF 2 ml. The mixture
was stirred at room temperature for 5 hr and allowed to stand
overnight at 4.degree. C. DMF 20 ml and KI 1.7 g were added thereto
under nitrogen atomosphere and the mixture was cooled to
-50.degree. C. AcCl 0.523 ml was added dropwise and the mixture was
stirred at -50.degree. C. for 1 hr and at -50.degree. C. to
-10.degree. C. for 1.5 hr. The reaction solution was added dropwise
to a 5% NaCl solution containing Na.sub.2S.sub.2O.sub.3 1 g under
ice-cooling to give precipitates. The precipitates were collected
by filtration and dried using P.sub.2O.sub.5 under reduced pressure
to give compound 14-2 (1.59 g) as powder.
[0237] Compound 14-2
[0238] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.40(9H, s), 1.46(18H,
s), 2.03(2H, m), 2.78(3H, brs), 3.18(2H, t, J=7.2 Hz), 3.27 and
3.43(2H, ABq, J=18.3 Hz), 3.75(3H, s), 4.43(2H, t, J=6.6 Hz),
4.55(2H, s), 5.18(1H, d, J=4.8 Hz), 5.21 and 5.28(2H, ABq, J=12.0
Hz), 5.65 and 5.73(2H, ABq, J=15.3 Hz), 5.95(1H, dd, J=4.8 and 8.7
Hz), 6.89(2H, d, J=8.7 Hz), 7.00(1H, d, J=3.3 Hz), 7.35(2H, d,
J=8.7 Hz), 7.78(1H, dd, J=6.3 and 8.1 Hz), 8.43(1H, d, J=3.3 Hz),
8.60(1H, d, J=6.3 Hz), 8.88(1H, d, J=8.1 Hz), 9.65(1H, d, J=8.7
Hz), 12.1(1H, brs).
[0239] IR (KBr) cm.sup.-1: 3427, 3058, 2976, 2933, 1791, 1718,
1686, 1630, 1613, 1584, 1550, 1515, 1496, 1455, 1393, 1368, 1300,
1247, 1156, 1080, 1063, 1022.
[0240] MS(ESI):
1039.sup.+(C.sub.48H.sub.60ClN.sub.8O.sub.12S.sub.2.sup.+)- .
[0241] Compound 11-2
[0242] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.44(9H, s), 1.53(9H, s),
3.47 and 3.63(2H, ABq, J=18.0 Hz), 3.82(3H, s), 4.45(2H, s), 4.68
and 4.75(2H, ABq, J=16.8 Hz), 5.05(1H, d, J=4.8 Hz), 5.20 and
5.27(2H, ABq, J=12.0 Hz), 5.98(1H, dd, J=4.8 and 9.3 Hz), 6.91(2H,
d, J=8.7 Hz), 7.35(2H, d, J=8.7 Hz), 8.11(1H, brs), 8.49(1H, d,
J=9.3 Hz).
[0243] IR (KBr) cm.sup.-1: 3382, 3277, 2979, 2935, 2837, 1791,
1722, 1613, 1551, 1515, 1455, 1369, 1302, 1246, 1157, 1085, 1062,
1036, 1021.
[0244] MS(FAB): 786.sup.+(M+H.sup.+).
[0245] HR-MS(FAB): calcd for
C.sub.32H.sub.38Cl.sub.2N.sub.5O.sub.10S.sub.- 2 786.1437 found
786.1434.
[0246] (2) Compound 14-2 (1.59 g, about 1.47 mmol) was deprotected
according to Example 5(3) to give compound 16-2 (I-3a-5d, 270
mg).
[0247] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.40(9H, s), 1.46(18H,
s), 2.03(2H, m), 2.78(3H, brs), 3.18(2H, t, J=7.2 Hz), 3.27 and
3.43(2H, ABq, J=18.3 Hz), 3.75(3H, s), 4.43(2H, t, J=6.6 Hz),
4.55(2H, s), 5.18(1H, d, J=4.8 Hz), 5.21 and 5.28(2H, ABq, J=12.0
Hz), 5.65 and 5.73(2H, ABq, J=15.3 Hz), 5.95(1H, dd, J=4.8 and 8.7
Hz), 6.89(2H, d, J=8.7 Hz), 7.00(1H, d, J=3.3 Hz), 7.35(2H, d,
J=8.7 Hz), 7.78(1H, dd, J=6.3 and 8.1 Hz), 8.43(1H, d, J=3.3 Hz),
8.60(1H, d, J=6.3 Hz), 8.88(1H, d, J=8.1 Hz), 9.65(1H, d, J=8.7
Hz), 12.1(1H, brs).
[0248] IR (KBr) cm.sup.-1: 3427, 3058, 2976, 2933, 1791, 1718,
1686, 1630, 1613, 1584, 1550, 1515, 1496, 1455, 1393, 1368, 1300,
1247, 1156, 1080, 1063, 1022.
[0249] MS(ESI):
1039.sup.+(C.sub.48H.sub.60ClN.sub.8O.sub.12S.sub.2.sup.+)- .
EXAMPLE 3
[0250] 50
[0251] I-3d-1
[0252] .sup.1H-NMR (D.sub.2O) .delta.: 1.54(6H, s), 3.22 and
3.64(2H, ABq, J=17.7 Hz), 5.28(1H, d, J=4.8 Hz), 5.34 and 5.58(2H,
ABq, J=14.4 Hz), 5.88(1H, d, J=4.8 Hz), 8.09(2H, t like), 8.58(1H,
t like), 8.96(2H, d, J=6.0 Hz).
[0253] IR (KBr) cm.sup.-1: 3417, 3058, 2989, 2938, 2524, 1778,
1673, 1625, 1536, 1486, 1386, 1340, 1157.
[0254] MS(ESI):581.sup.+(M+H.sup.+).
[0255] Elemental analysis
C.sub.22H.sub.21ClN.sub.6O.sub.7S.sub.2.multidot- .2.9H.sub.2O.
[0256] Calc.: C, 41.73; H, 4.27; N, 13.27; Cl, 5.60; S, 10.13 (%).
Found: C, 41.74; H, 3.99; N, 13.16; Cl, 5.53; S, 10.20 (%).
[0257] Quaternary Salt Ester:
[0258] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37(9H, s), 1.42(3H,
s), 1.44(3H, s), 1.46(9H, s), 3.51(2H, brs), 3.77(3H, s), 5.20 and
5.26(2H, ABq, J=12.0 Hz), 5.22(1H, d, J=5.1 Hz), 5.58(2H, brs),
5.98(1H, dd, J=5.1 and 9.0 Hz), 6.93(2H, d, J=8.4 Hz), 7.35(2H, d,
J=8.4 Hz), 8.20(2H, t like), 8.66(1H, t like), 8.99(2H, d, J=5.7
Hz), 9.57(1H, d, J=9.0 Hz), 12.1(1H, brs).
[0259] IR (KBr) cm.sup.-1: 3428, 3054, 2979, 2935, 1791, 1718,
1629, 1614, 1548, 1515, 1481, 1455, 1392, 1369, 1299, 1247, 1153,
1064, 1029.
[0260] MS(ESI):
857.sup.+(C.sub.39H.sub.46ClN.sub.6O.sub.10S.sub.2.sup.+).
EXAMPLE 4
[0261] 51
[0262] I-3d-2a:
[0263] .sup.1H-NMR (D2O) .delta.: 1.40(6H, s), 3.18 and 3.55(2H,
ABq, J=17.7 Hz), 4.88 and 5.02(2H, ABq, J=14.7 Hz), 5.23(1H, d,
J=4.8 Hz), 5.84(1H, d, J=4.8 Hz), 6.83 and 8.05(4H, A2B2q,
J=7.5).
[0264] IR (KBr) cm.sup.-1: 3400, 3189, 2993, 1770, 1654, 1604,
1537, 1398, 1361, 1165.
[0265] Elemental analysis
C.sub.27H.sub.21.2N.sub.7O.sub.7S.sub.2ClNa.sub.-
0.8.multidot.5H.sub.2O .iota..tau..
[0266] Calc.: C, 37.55; H, 4.47; N, 13.93; S, 9.11; Cl, 5.04; Na,
2.61 (%). Found: C, 37.34; H, 4.28; N, 13.73; S, 9.07; Cl, 4.97;
Na, 2.70 (%).
[0267] Quaternary Salt Ester:
[0268] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.43(9H, s), 1.51(9H, s),
1.55(9H, s), 1.58(3H, s), 1.59(3H, s), 3.35 and 3.92(2H, ABq,
J=19.2 Hz), 3.82(3H, s), 5.24.about.5.30(3H, m), 5.31 and 5.57(2H,
Abq, J=14.4 Hz), 6.01(1H, dd, J=4.8, 8.7 Hz), 6.90 and 7.36(4H,
A2B2q, J=9 Hz), 8.04.about.8.12(3H, m), 8.35(1H, br s), 8.63(2H,
J=7.5 Hz), 8.98(1H, s).
[0269] IR (KBr) cm.sup.-1: 3422, 3274, 2979, 2934, 1794, 1719,
1641, 1530, 1457, 1369, 1299, 1246, 1146, 842.
EXAMPLE 5
[0270] 52
[0271] (1) To a solution of compound 4-1 (10.3, 22.2 mmol) obtained
in Reference Example 1 and compound 10 (9.90 g 24.4 mmol) in dry
DMA 100 ml, were added WSCD.multidot.HCl (5.11 g 1.2 eq) and
pyridine (1.80 ml, 1.0 eq) under ice-cooling and the mixture was
stirred at room temperature for 1 hr. The reaction mixture was
poured to ice water 300 ml and extracted with AcOE (200
ml.times.2). The obtained organic layer washed with brine, dried
over anhydrous MgSO.sub.4, and concentrated in vacuum. Purification
with silica gel column chromatography, followed by concentration in
vacuum, gave compound 11-1 (13.7 g) as foam.
[0272] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.42(9H, s), 1.52(9H, s),
1.60(6H, s), 3.48 and 3.65(2H, ABq, J=18.0 Hz), 3.82(3H, s), 4.45
and 4.55(2H, ABq, J=11.7 Hz), 5.04(1H, d, J=5.1 Hz), 5.20 and
5.27(2H, ABq, J=12.0 Hz), 6.03(1H, dd, J=5.1 and 9.3 Hz), 6.91(2H,
d, J=8.7 Hz), 7.35(2H, d, J=8.7 Hz), 8.03(1H, d, J=9.3 Hz),
8.13(1H, brs).
[0273] IR (KBr) cm.sup.-1: 3396, 3284, 2979, 2937, 2836, 1791,
1722, 1614, 1550, 1515, 1455, 1384, 1369, 1301, 1247, 1155,
1035.
[0274] MS(ESI): 814.sup.+(M+H.sup.+).
[0275] Elemental analysis
C.sub.34H.sub.41Cl.sub.2N.sub.5O.sub.10S.sub.2.m- ultidot.0.2
CHCl.sub.3.multidot.0.4H.sub.2O.
[0276] Calc.: C, 48.56; H, 5.00; N, 8.28; S, 7.58; Cl, 10.90 (%).
Found: C, 48.51; H, 4.85; N, 8.11; S, 7.56; Cl, 11.00 (%).
[0277] (2) To a solution of compound 11-1 (5.0 g 6.14 mmol) in THF
50 ml which was cooled to 15.degree. C. under nitrogen atomosphere,
was added NaI 2.76 g (3 eq) and the mixture was stirred at
15.degree. C. for 30 min. The reaction solution was poured to ice
water 150 ml and extracted with AcOE. The obtained organic layer
was washed with a saturated Na.sub.2S.sub.2O.sub.3 aq. solution and
brine, dried over anhydrous MgSO.sub.4, and concentrated under
reduced pressure to give compound 12 (5.51 g) as a form. To a
solution of compound 12 (2.72 g 3.0 mmol) in DMF 12 ml, was added a
solution of compound 13 (868 mg 1 eq) in DMF 3 ml under nitrogen
atomosphere. After stirring at room temperature for 1 hr, the
reaction mixture was added dropwise to a 5% NaCl solution under
ice-cooling to give pale yellow precipitates, which was collected
by filtration. Drying with P.sub.2O.sub.5 under reduced pressure
gave compound 14-1 (3.26 g) as powder.
[0278] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37(9H, s), 1.43(6H,
s), 1.46(18H, s), 2.03(2H, m), 2.78(3H, brs), 3.17(2H, m), 3.28 and
3.39(2H, ABq, J=16.2 Hz), 3.76(3H, s), 4.43(2H, m), 5.18(1H, d,
J=5.1 Hz), 5.22 and 5.30(2H, ABq, J=11.7 Hz), 5.70(2H, brs),
5.95(1H, dd, J=5.1 and 8.7 Hz), 6.90(2H, d, J=8.7 Hz), 6.95(1H, d,
J=3.3 Hz), 7.33(2H, d, J=8.7 Hz), 7.78(1H, dd, J=5.7 and 8.4 Hz),
8.43(1H, d, J=3.3 Hz), 8.63(1H, d, J=5.7 Hz), 8.88(1H, d, J=8.4
Hz), 9.58(1H, d, J=8.7 Hz), 12.1(1H, brs).
[0279] IR (KBr) cm.sup.-1: 3423, 2977, 2935, 1789, 1718, 1685,
1629, 1612, 1550, 1515, 1496, 1455, 1392, 1367, 1299, 1249,
1153.
[0280] MS(ESI):
1067.sup.+(C.sub.50H.sub.64ClN.sub.8O.sub.12S.sub.2.sup.+)- .
[0281] (3) To a solution of compound 14-1 (3.20 g) in MeNO.sub.2 30
ml and anisole 30 ml, was added a AlCl.sub.3-MeNO.sub.2 solution
(1.5M, 21 ml) in nitrogen atomosphere under ice-cooling and the
mixture was stirred for 1 hr. Ice, 1N HCl, CH.sub.3CN and Et.sub.2O
were added thereto, and the water layer was separated and
concentrated in vacuum. Purification with HP-20 chromato, followed
by lyophilization, gave compound 16-1 (I-3d-5d, colorless powder,
900 mg).
[0282] .sup.1H-NMR (D.sub.2O) .delta.: 2.30(2H, m), 2.68(3H, s),
3.05(2H, m), 3.15 and 3.38 (2H, ABq, J=17.7 Hz), 4.52(2H, t, J=6.9
Hz), 4.54(2H, s), 5.16(1H, d, J=4.8 Hz), 5.56 and 5.67(2H, ABq,
J=15.0 Hz), 5.83(1H, d, J=4.8 Hz), 7.04(1H, d, J=3.6 Hz), 7.68(1H,
dd, J=6.0 and 8.1 Hz), 8.12(1H, d, J=3.6 Hz), 8.59(1H, d, J=8.1
Hz), 8.65(1H, d, J=6.0 Hz).
[0283] IR (KBr) cm.sup.-1: 3394, 2817, 1773, 1604, 1539, 1498,
1466, 1391, 1361, 1317, 1163, 1121, 1055, 1033.
[0284] MS(ESI):663.sup.+(M+H.sup.+).
[0285] Elemental analysis C.sub.26H.sub.27ClN.sub.8O.sub.7S.sub.2
3.7H.sub.2O.
[0286] Calc.: C, 42.79; H, 4.75; N, 15.35; Cl, 4.86; S, 8.79 (%).
Found: C, 42.78; H, 4.66; N, 15.42; Cl, 4.81; S, 9.02 (%).
EXAMPLE 6
[0287] 53
[0288] I-3d-6d:
[0289] .sup.1H-NMR(D.sub.6-DMSO-D.sub.2O) .delta.:1.38(6H, brs),
2.23(2H, brs), 2.48(3H, s), 2.92(2H, brs), 3.13 and 3.52 (2H, ABq,
J=17.4 Hz), 4.55(2H, brs), 5.06(1H, d, J=4.8 Hz), 5.59 and 5.70(2H,
ABq, J=12.9 Hz), 5.79(1H, d, J=4.8 Hz), 7.71(1H, t like), 8.82(1H,
d, J=7.8), 9.04(1H, s), 9.19(1H, d, J=5.1 Hz).
[0290] IR(KBr) cm.sup.-1: 3421, 2460, 1772, 1610, 1538, 1488, 1465,
1394, 1359, 1315, 1234, 1159.
[0291] MS(ESI):692.sup.+(M+H.sup.+).
[0292] Elemental analysis
C.sub.27H.sub.30ClN.sub.9O.sub.7S.sub.2.multidot-
.5.3(H.sub.2O).
[0293] Calc.: C, 40.98; H, 5.18; N, 15.93; Cl, 4.93; S, 8.10 (%).
Found: C, 40.70; H, 4.88; N, 15.74; Cl, 4.94; S, 7.97 (%).
EXAMPLE 7
[0294] 54
[0295] I-3d-5c:
[0296] .sup.1H-NMR (D.sub.2O) .delta.: 1.48(6H, s), 2.73(3H, s),
3.17 and 3.40(2H, ABq, J=17.7 Hz), 3.61(2H, t, J=6.0 Hz), 4.79(2H,
t, J=6.0 Hz), 5.17(1H, d, J=5.1 Hz), 5.57 and 5.69(2H, ABq, J=15.0
Hz), 5.81(1H, d, J=5.1 Hz), 7.10(1H, d, J=3.3 Hz), 7.70(1H, dd,
J=6.3 and 8.1 Hz), 8.14(1H, d, J=3.3 Hz), 8.61(1H, d, J=8.1 Hz),
8.69(1H, d, J=6.3 Hz).
[0297] IR (KBr) cm.sup.-1: 3401, 2987, 2451, 1772, 1606, 1538,
1500, 1467, 1396, 1361, 1288, 1159, 1120.
[0298] MS(ESI):677.sup.+(M+H.sup.+).
[0299] Elemental analysis
C.sub.27H.sub.29ClN.sub.8O.sub.7S.sub.2.multidot- .6.5H.sub.2O.
[0300] Calc.: C, 40.83; H, 5.33; N, 14.11; Cl, 4.46; S, 8.07 (%).
Found: C, 40.82; H, 5.14; N, 14.12; Cl, 4.57; S, 8.03 (%).
[0301] Quaternary Salt Ester:
[0302] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37(9H, s), 1.39(3H,
s), 1.43(3H, s), 1.46(18H, s), 2.80(3H, brs), 3.27 and 3.39(2H, m),
3.59(2H, m), 3.76(3H, s), 4.60(2H, brs), 5.17(1H, d, J=5.1 Hz),
5.23 and 5.31(2H, ABq, J=12.0 Hz), 5.72(2H, brs), 5.96(1H, dd,
J=5.1 and 8.7 Hz), 6.92(2H, d, J=8.4 Hz), 7.02(1H, d, J=3.6 Hz),
7.36(2H, d, J=8.4 Hz), 7.82(1H, m), 8.31(1H, d, J=3.6 Hz), 8.67(1H,
m), 8.85(1H, m), 9.58(1H, d, J=8.7 Hz), 12.1(1H, brs).
EXAMPLE 8
[0303] 55
[0304] I-3e-5d
[0305] .sup.1H-NMR (D.sub.2O) .delta.: 1.40(3H, d, J=6.9 Hz),
2.31(2H, q like), 2.68(3H, s), 3.05(2H, t like), 3.14 and 3.39(2H,
ABq, J=17.7 Hz), 4.52(2H, t like), 4.61(1H, q, J=6.9 Hz), 5.19(1H,
d, J=4.8 Hz), 5.57 and 5.67(2H, ABq, J=15 Hz), 5.80(1H, d, J=4.5
Hz), 7.06(1H, d, J=3.6), 7.69(1H, dd, J=6.0, 8.1 Hz), 8.12(1H, d,
J=3.6 Hz), 8.59(1H, d, J=8.1 Hz), 8.64(1H, d, J=6.0 Hz).
[0306] IR (KBr) cm.sup.-1: 3411, 1774, 1606, 1539, 1498, 1392,
1363, 1034, 759.
[0307] Positive ESIMS: m/z 677 [M+H]+. Negative ESIMS: m/z 675
[M-H]-.
[0308] Elemental analysis as
C.sub.27H.sub.29N.sub.8O.sub.7S.sub.2Cl.multi- dot.6.2H.sub.2O
[0309] Calc.: C, 41.11; H, 5.29; N, 14.20; S, 8.13; Cl, 4.49 (%).
Found: C, 40.99; H, 5.07; N, 14.15; S, 8.21; Cl, 4.76 (%).
[0310] Quaternary Salt Ester:
[0311] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.48(9H, s), 1.51(9H, s),
1.60(3H, d, J=7.2 Hz), 2.22(2H, t like), 2.91(3H, s), 3.17 and
3.73(2H, ABq, J=18.6 Hz), 3.37(2H, t like), 3.81(3H, s), 4.44(2H, t
like), 5.03(1H, q, J=7.2 Hz), 5.17(1H, d, J=5.1 Hz), 5.24 and
5.30(2H, ABq, J=11.7 Hz), 5.63 and 5.75(2H, ABq, J=15 Hz), 6.01(1H,
dd, J=5.1, 9 Hz), 6.87 (2H, d, J=8.7 Hz), 6.88(1H, s),
7.24.about.7.35 (12H, m), 7.59(1H, dd, J=6, 8.1 Hz), 7.78(1H, d,
J=9 HZ), 8.24(1H, m), 8.34(1H, br s), 8.48(1H, d, J=8.1 Hz),
8.53(1H, d, J=6.0 Hz).
[0312] IR (KBr) cm.sup.-1: 3430, 3091, 3060, 1793, 1718, 1684,
1630, 1549, 1516, 1367, 1247, 1153, 1034, 754, 702.
[0313] 3-Chloromethyl Compound:
[0314] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.53(9H, s), 1.65(3H, d,
J=7.2 Hz), 3.23 and 3.47(2H, ABq, J=18.3 Hz), 3.82(3H, s), 4.39 and
4.55(2H, ABq, J=12 Hz), 4.99(1H, d, J=5.1 Hz), 5.10(1H, q, J=7.2
Hz), 5.21 and 5.27(2H, ABq, J=12 Hz), 5.99(1H, dd, J=5.1, 9.9 Hz),
6.91(3H, m), 7.16.about.7.37 (12H, m), 7.76 (1H,d, J=9.9 Hz),
8.20(1H, br s).
[0315] IR (KBr) cm.sup.-1: 3373, 3286, 2979, 2937, 1791, 1720,
1612, 1550, 1515, 1248, 1155, 1035, 700.
[0316] 7-Side Chain (NEt.sub.3 Salt):
[0317] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.50(9H, s), 1.51(3H, d,
J=7.2 Hz), 4.94(1H, q, J=7.2), 6.89(1H, s), 7.23.about.7.35(10H,
m).
[0318] IR (KBr) cm.sup.-1: 3429, 2981, 2937, 1739, 1714, 1612,
1556, 1250, 1157, 1036, 964, 700,
[0319] Positive ESIMS: m/z 560[M+H]+, m/z 582[M+Na]+. Negative
ESIMS: m/z 558[M-H]-, m/z 580[M+Na-2H]-.
EXAMPLE 9
[0320] 56
[0321] I-3f-5d:
[0322] .sup.1H-NMR (D2O) .delta.: 1.43 (3H, d, J=7.2 Hz), 2.31(2H,
q like), 2.68(3H, s), 3.05(2H, t, J=8 Hz), 3.18 and 3.37(2H, ABq,
J=18 Hz), 4.53(2H, t like), 4.65 (1H, q, J=7.2 Hz), 5.17(1H, d,
J=4.8 Hz), 5.54 and 5.70(2H, ABq, J=15 Hz), 5.86(1H, d, J=4.5 Hz),
7.03(1H, d, J=3.6 Hz), 7.69(1H, dd, J=6, 8.4 Hz), 8.13(1H, d, J=3.6
Hz), 8.60(1H, d, J=8.4 Hz), 8.64(1H, d, J=6 Hz).
[0323] IR (KBr) cm.sup.-1: 3398, 1775, 1603, 1541, 1392, 1363,
1320, 1286, 1033, 762.
[0324] Positive ESIMS: m/z 677 [M+H]+. Negative ESIMS: m/z 675
[M-H]-.
[0325] Elemental analysis as
C.sub.27H.sub.29N.sub.8O.sub.7S.sub.2Cl.multi- dot.6.2H.sub.2O.
[0326] Calc.: C, 41.11; H, 5.29; N, 14.20; S, 8.13; Cl, 4.49 (%).
Found: C, 40.88; H, 4.88; N, 14.23; S, 8.05; Cl, 4.57 (%).
[0327] Quaternary Salt Ester:
[0328] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.48(9H, s), 1.51(9H, s),
1.62(3H, d, J=7.2 Hz), 2.21(2H, m), 2.91(3H, s), 3.24 and 3.82(2H,
ABq, J=18.9 Hz), 3.36(2H, m), 3.81(3H, s), 4.43(2H, t like),
5.09(1H, q, J=7.2 Hz), 5.16(1H, d, J=5.1 Hz), 5.24 and 5.31(2H,
ABq, J=11.7 Hz), 5.58 and 5.75(2H, ABq, J=14.7 Hz), 5.99(1H, dd,
J=5.1, 8.7 Hz), 6.86(1H, s), 6.87(2H, d, J=8.7 Hz), 7.00(1H, br s),
7.24-7.38(12H, m), 7.55(1H, t like), 7.78(H, d, J=8.7 Hz), 8.25(1H,
br s), 8.47(1H, d, J=10.2 Hz), 8.50(1H, d, J=6 Hz).
[0329] 3-Chloromethyl Compound:
[0330] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.53(9H, s), 1.64(6H, d,
J=7.2 Hz), 3.39 and 3.58(2H, ABq, J=18.3 Hz), 3.81(3H, s), 4.42 and
4.59(2H, ABq, J=12 Hz), 4.97(1H, d, J=5.1 Hz), 5.08(1H, q, J=7.2
Hz), 5.20 and 5.27(2H, ABq, J=11.7 Hz), 6.01(1H, dd, J=5.1, 9.3
Hz), 6.88-6.91(3H, m), 7.06-7.35(12H, m), 7.85(1H, d, J=9.3 Hz),
8.15(1H, br s).
[0331] IR (KBr) cm.sup.-1: 3281, 2980, 2935, 2836, 1790, 1719,
1612, 1552, 1515, 1454, 1369, 1247, 1155, 1035, 700.
[0332] 7-Side Chain:
[0333] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.47(9H, s), 1.49(3H,
J=7.2 Hz), 4.99(1H, q, J=7.2 Hz).
EXAMPLE 10
[0334] 57
[0335] I-3g-5d
[0336] .sup.1H-NMR (D.sub.2O) .delta.: 0.90(3H, t, J=7.5 Hz),
1.79(2H, quintet-like), 2.31(2H, quintet-like), 2.69(3H, s),
3.05(2H, t, J=8.1 Hz), 3.12 and 3.39 (2H, ABq, J=18.0 Hz), 4.45(1H,
t, J=6.6 Hz), 4.52(2H, t, J=7.2 Hz), 5.19(1H, d, J=4.8 Hz), 5.58
and 5.66(2H, ABq, J=14.7 Hz), 5.78(1H, d, J=4.8 Hz), 7.06(1H, d,
J=3.3 Hz), 7.69(1H, dd, J=6.0 and 8.1 Hz), 8.12(1H, d, J=3.3 Hz),
8.59(1H, d, J=8.1 Hz), 8.65(1H, d, J=6.0 Hz).
[0337] IR (KBr) cm.sup.-1: 3397, 2967, 1774, 1604, 1537, 1497,
1459, 1390, 1361, 1315, 1159, 1120, 1051, 1031.
[0338] MS(ESI):691.sup.+(M+H.sup.+).
[0339] Elemental analysis as
C.sub.28H.sub.31ClN.sub.8O.sub.7S.sub.2.multi- dot.4.9H.sub.2O.
[0340] Calc.: C, 43.15; H, 5.28; N, 14.38; Cl, 4.55; S, 8.23 (%).
Found: C, 43.02; H, 5.01; N, 14.51; Cl, 4.54; S, 8.27 (%).
[0341] Quaternary Salt Ester:
[0342] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 0.90(3H, t, J=7.2 Hz),
1.36(9H, brs), 1.45(9H, s), 1.85(2H, quintet-like), 2.03(2H,
quintet-like), 2.78(3H, brs), 3.18(2H, t, J=6.9 Hz), 3.28 and
3.34(2H, ABq, J=15.9 Hz), 3.75(3H, s), 4.43(2H, t, J=6.9 Hz),
4.71(1H, t, J=6.6 Hz), 5.18(1H, d, J=4.8 Hz), 5.21 and 5.30(2H,
ABq, J=11.7 Hz), 5.66 and 5.72(2H, ABq, J=15.6 Hz), 5.99(1H, dd,
J=4.8 and 9.0 Hz), 6.84(1H, s), 6.88(2H, d, J=8.7 Hz), 6.97(1H, d,
J=3.6 Hz), 7.20-7.44(12H, m), 7.76(1H, dd, J=6.3 and 8.1 Hz),
8.42(1H, d, J=3.6 Hz), 8.60(1H, d, J=6.3 Hz), 8.88(1H, d, J=8.1
Hz), 9.69(1H, d, J=9.0 Hz), 12.1(1H, brs).
[0343] IR (KBr) cm.sup.-1: 3414, 3062, 3032, 2975, 2935, 1791,
1717, 1686, 1630, 1613, 1585, 1550, 1515, 1495, 1455, 1393, 1367,
1248, 1154, 1018.
[0344] MS(ESI): 924.sup.+(M+H.sup.+).
[0345] 3-Chloromethyl Compound:
[0346] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.08(3H, t, J=7.2 Hz),
1.53(9H, s), 1.90-2.10(2H, m), 3.26 and 3.50(2H, ABq, J=18.3 Hz),
3.82(3H, s), 4.40 and 4.56(2H, ABq, J=11.7 Hz), 4.91(1H, dd, J=5.1
and 9.0 Hz), 4.99(1H, d, J=5.1 Hz), 5.21 and 5.28(2H, ABq, J=11.7
Hz), 5.98(1H, dd, J=5.1 and 9.6 Hz), 6.91(2H, d, J=8.7 Hz),
6.93(1H, s), 7.25-7.32(10H, m), 7.36(2H, d, J=8.7 Hz), 7.72(1H, d,
J=9.6 Hz), 8.01(1H, brs).
[0347] IR (KBr) cm.sup.-1: 3378, 3291, 3063, 3032, 2975, 2935,
1791, 1721, 1613, 1550, 1515, 1455, 1384, 1368, 1301, 1246, 1155,
1109, 1058, 1032, 1003.
[0348] 7-Side Chain
[0349] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 0.89(3H, t, J=7.5 Hz),
1.46(9H, s), 1.78(2H, quintet like), 4.52(1H, t, J=6.9 Hz),
6.84(1H, s), 7.23-7.46(10H, m), 12.0(1H, brs).
[0350] IR (KBr) cm.sup.-1: 3428, 3164, 3063, 3032, 2978, 2936,
1717, 1623, 1557, 1496, 1455, 1392, 1370, 1292, 1251, 1210, 1157,
1105, 1056, 1036.
[0351] MS(ESI): 574.sup.+(M+H.sup.+).
EXAMPLE 11
[0352] 58
[0353] I-3h-5d:
[0354] .sup.1H-NMR (D.sub.2O) .delta.: 0.93(3H, t, J=7.5 Hz),
1.83(2H, quintet-like), 2.30(2H, quintet-like), 2.69(3H, s),
3.05(2H, t, J=8.1 Hz), 3.16 and 3.37 (2H, ABq, J=17.7 Hz), 4.52(1H,
t, J=6.0 Hz), 4.52(2H, t, J=6.3 Hz), 5.17(1H, d, J=4.8 Hz), 5.55
and 5.68(2H, ABq, J=15.0 Hz), 5.85(1H, d, J=4.8 Hz), 7.03(1H, d,
J=3.6 Hz), 7.69(1H, dd, J=6.0 and 8.4 Hz), 8.12(1H, d, J=3.6 Hz),
8.58(1H, d, J=8.4 Hz), 8.64(1H, d, J=6.0 Hz).
[0355] IR (KBr) cm.sup.-1: 3388, 2970, 1775, 1602, 1539, 1498,
1463, 1392, 1362, 1316, 1160, 1121, 1061, 1032.
[0356] MS(ESI):691.sup.+(M+H.sup.+).
[0357] Elemental analysis as
C.sub.28H.sub.31ClN.sub.8O.sub.7S.sub.2.multi- dot.5.6H.sub.2O.
[0358] Calc.: C, 42.46; H, 5.37; N, 14.15; Cl, 4.48; S, 8.10 (%).
Found: C, 42.38; H, 5.02; N, 14.25; Cl, 4.41; S, 8.02 (%).
[0359] Quaternary Salt Ester:
[0360] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 0.86(3H, t, J=7.2 Hz),
1.36(9H, brs), 1.46(9H, s), 1.83(2H, quintet-like), 2.03(2H,
quintet-like), 2.77(3H, brs), 3.18(2H, t, J=6.9 Hz), 3.29 and
3.39(2H, ABq, J=18.9 Hz), 3.76(3H, s), 4.43(2H, t, J=6.6 Hz),
4.73(1H, t, J=6.6 Hz), 5.19(1H, d, J=4.8 Hz), 5.21 and 5.30(2H,
ABq, J=11.7 Hz), 5.70(2H, brs), 5.98(1H, dd, J=4.8 and 8.7 Hz),
6.84(1H, s), 6.89(2H, d, J=9.0 Hz), 6.96(1H, d, J=3.0 Hz),
7.20-7.44(12H, m), 7.78(1H, dd, J=6.3 and 8.4 Hz), 8.42(1H, d,
J=3.0 Hz), 8.60(1H, d, J=6.3 Hz), 8.88(1H, d, J=8.4 Hz), 9.74(1H,
d, J=8.7 Hz), 12.1(1H, brs).
[0361] IR (KBr) cm.sup.-1: 3423, 3061, 3032, 2974, 2934, 1791,
1718, 1686, 1630, 1613, 1585, 1549, 1515, 1495, 1455, 1392, 1367,
1247, 1154, 1123, 1060, 1029.
[0362] MS(ESI):
1177.sup.+(C.sub.59H.sub.66ClN.sub.8O.sub.12S.sub.2.sup.+)- .
[0363] 3-Chloromethyl Compound:
[0364] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.02(3H, t, J=7.2 Hz),
1.53(9H, s), 1.96-2.08(2H, m), 3.40 and 3.59(2H, ABq, J=18.0 Hz),
3.81(3H, s), 4.43 and 4.58(2H, ABq, J=11.7 Hz), 4.93(1H, t, J=6.3
Hz), 4.99(1H, d, J=5.1 Hz), 5.20 and 5.28(2H, ABq, J=11.7 Hz),
6.01(1H, dd, J=5.1 and 9.0 Hz), 6.90(2H, d, J=9.0 Hz), 6.95(1H, s),
7.25-7.31(10H, m), 7.35(2H, d, J=9.0 Hz), 7.91(1H, d, J=9.0 Hz),
7.93(1H, brs).
[0365] IR (KBr) cm.sup.-1: 3283, 3063, 3031, 2976, 2936, 2836,
1791, 1721, 1613, 1550, 1515, 1455, 1384, 1369, 1301, 1246, 1155,
1058, 1033, 1004.
[0366] MS(ESI): 924.sup.+(M+H.sup.+).
[0367] Elemental analysis as
C.sub.43H.sub.43Cl.sub.2N.sub.5O.sub.10S.sub.- 2.multidot.0.3
CHCl.sub.3.multidot.0.8H.sub.2O.
[0368] Calc.: C, 53.33; H, 4.64; N, 7.18; S, 6.58; Cl, 10.54
(%).
[0369] 7-Side Chain
[0370] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 0.89(3H, t, J=7.5 Hz),
1.46(9H, s), 1.78(2H, quintet like), 4.52(1H, t, J=6.9 Hz),
6.84(1H, s), 7.23-7.46(10H, m), 12.0(1H, brs).
[0371] IR (KBr) cm.sup.-1: 3431, 3180, 3064, 3033, 2978, 2934,
1736, 1715, 1621, 1557, 1496, 1455, 1391, 1370, 1295, 1250, 1211,
1158, 1118, 1064, 1034.
[0372] MS(ESI): 574.sup.+(M+H.sup.+).
EXAMPLE 12
[0373] 59
[0374] I-3i-5d:
[0375] .sup.1H-NMR (D.sub.2O) .delta.: 0.93(6H, d, J=6.9 Hz),
2.09(1H, sextet-like), 2.31(2H, quintet-like), 2.68(3H, s),
3.04(2H, t, J=8.1 Hz), 3.13 and 3.39 (2H, ABq, J=17.7 Hz), 4.27(1H,
d, J=6.0 Hz), 4.53(2H, t, J=6.9 Hz), 5.19(1H, d, J=4.8 Hz), 5.58
and 5.66(2H, ABq, J=15.0 Hz), 5.80(1H, d, J=4.8 Hz), 7.07(1H, d,
J=3.3 Hz), 7.69(1H, dd, J=6.3 and 8.7 Hz), 8.12(1H, d, J=3.3 Hz),
8.60(1H, d, J=8.7 Hz), 8.65(1H, d, J=6.3 Hz).
[0376] IR (KBr) cm.sup.-1: 3396, 2965, 1775, 1604, 1538, 1498,
1466, 1391, 1364, 1223, 1121, 1062, 1027.
[0377] MS(ESI):705.sup.+(M+H.sup.+).
[0378] Elemental analysis as
C.sub.29H.sub.33ClN.sub.8O.sub.7S.sub.2.multi-
dot.4.28H.sub.2O.
[0379] Calc.: C, 44.52; H, 5.35; N, 14.32; Cl, 4.53; S, 8.20 (%).
Found: C, 44.14; H, 4.96; N, 14.38; Cl, 4.53; S, 8.14 (%).
[0380] Quarternary Ammonium Salt Ester:
[0381] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 0.88(3H, d, J=6.9 Hz),
0.90(3H, d, J=6.6 Hz), 1.36(9H, brs), 1.45(9H, s), 2.02(2H,
quintet-like), 2.15(1H, sextet-like), 2.77(3H, brs), 3.17(2H, t,
J=6.9 Hz), 3.26 and 3.40(2H, ABq, J=18.3 Hz), 3.75(3H, s), 4.42(2H,
t-like), 4.50(1H, t, J=6.3 Hz), 5.18(1H, d, J=5.1 Hz), 5.20 and
5.30(2H, ABq, J=11.7 Hz), 5.65 and 5.71(2H, ABq, J=15.6 Hz),
6.00(1H, dd, J=5.1 and 8.4 Hz), 6.86(1H, s), 6.87(2H, d, J=8.4 Hz),
6.97(1H, d, J=3.3 Hz), 7.20-7.45(12H, m), 7.75(1H, dd, J=6.0 and
7.8 Hz), 8.41(1H, d, J=3.3 Hz), 8.58(1H, d, J=6.0 Hz), 8.87(1H, d,
J=7.8 Hz), 9.72(1H, d, J=8.4 Hz), 12.1(1H, brs).
[0382] IR (KBr) cm.sup.-1: 3393, 3061, 3031, 2972, 2933, 1791,
1719, 1686, 1630, 1613, 1550, 1515, 1495, 1455, 1392, 1367, 1248,
1175, 1155, 1125, 1029.
[0383] 3-Chloromethyl Compound:
[0384] .sup.1H-NMR (CDCl.sub.3) .delta.: 0.99(3H, d, J=7.2 Hz),
1.02(3H, d, J=7.2 Hz), 1.53(9H, s), 2.37(1H, sextet-like), 3.35 and
3.55(2H, ABq, J=18.3 Hz), 3.82(3H, s), 4.42 and 4.54(2H, ABq,
J=12.0 Hz), 4.76(1H, d, J=6.0 Hz), 4.99(1H, d, J=5.1 Hz), 5.21 and
5.28(2H, ABq, J=11.7 Hz), 5.95(1H, dd, J=5.1 and 9.3 Hz), 6.91(2H,
d, J=8.7 Hz), 6.94(1H, s), 7.25-7.32(10H, m), 7.36(2H, d, J=8.7
Hz), 7.51(1H, d, J=9.3 Hz), 8.03(1H, brs).
[0385] IR (KBr) cm.sup.-1: 3292, 3063, 3031, 2970, 2935, 2876,
2836, 1792, 1722, 1613, 1550, 1515, 1454, 1387, 1369, 1333, 1302,
1247, 1155, 1096, 1031.
[0386] MS(ESI): 938.sup.+(M+H.sup.+).
[0387] 7-Side Chain
[0388] .sup.1H-NMR(D.sub.6-DMSO) .delta.:0.83(3H, d, J=6.9 Hz),
0.93(3H, d, J=6.6 Hz), 1.46(9H, s), 2.05(1H, sex., J=ca 6.9 Hz),
4.28(1H, d, J=7.2 Hz), 6.86(1H, s), 7.24-7.31(6H, m), 7.43-7.45(4H,
m).
[0389] IR(KBr) cm.sup.-1:3431, 2971, 2934, 1740, 1715, 1619, 1555,
1371, 1251, 1157, 1034, 699.
EXAMPLE 13
[0390] 60
[0391] I-3j-5d:
[0392] .sup.1H-NMR (D.sub.2O) .delta.: 0.94(3H, d, J=7.2 Hz),
0.98(3H, d, J=6.9 Hz), 2.13(1H, sextet-like), 2.31(2H,
quintet-like), 2.68(3H, s), 2.91(2H, t, J=7.8 Hz), 3.15 and 3.37
(2H, ABq, J=17.7 Hz), 4.35(1H, d, J=5.4 Hz), 4.52(2H, t, J=6.9 Hz),
5.17(1H, d, J=4.8 Hz), 5.55 and 5.67(2H, ABq, J=15.3 Hz), 5.87(1H,
d, J=4.8 Hz), 7.04(1H, d, J=3.3 Hz), 7.69(1H, dd, J=6.0 and 8.1
Hz), 8.12(1H, d, J=3.3 Hz), 8.59(1H, d, J=8.1 Hz), 8.64(1H, d,
J=6.0 Hz).
[0393] IR (KBr) cm.sup.-1:3389, 2965, 1777, 1601, 1539, 1498, 1466,
1391, 1364, 1223, 1120, 1062, 1019.
[0394] MS(ESI):705.sup.+(M+H.sup.+).
[0395] Elemental analysis as
C.sub.29H.sub.33ClN.sub.8O.sub.7S.sub.2.multi- dot.6.5H.sub.2O.
[0396] Calc.: C, 42.36; H, 5.64; N, 13.63; Cl, 4.31; S, 7.80 (%).
Found: C, 42.01; H, 4.82; N, 13.51; Cl, 4.26; S, 7.89 (%).
[0397] 7-Side Chain
[0398] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 0.85(3H, d, J=6.6 Hz),
0.93(3H, d, J=6.6 Hz), 1.46(9H, s), 2.07(1H, sextet-like), 4.35(1H,
d, J=7.2 Hz), 6.87(1H, s), 7.1-7.5(11H, m), 12.0(1H, brs).
[0399] IR (KBr) cm.sup.-1: 3422, 3207, 3064, 3032, 2976, 2933,
2876, 1717, 1629, 1555, 1495, 1455, 1393, 1370, 1295, 1248, 1156,
1055, 1032.
[0400] MS(ESI):588.sup.+(M+H.sup.+).
[0401] Elemental analysis as
C.sub.28H.sub.30ClN.sub.8O.sub.7S.sub.1.multi-
dot.1.04H.sub.2O.multidot.0.12 AcOEt.
[0402] Calc.: C, 55.41; H, 5.39; N, 6.81; Cl, 5.74; S, 5.19 (%).
Found: C, 55.44; H, 5.11; N, 7.20; Cl, 5.67; S, 4.80 (%).
[0403] 3-Chloromethyl Compound:
[0404] .sup.1H-NMR (CDCl.sub.3) .delta.: 0.95(3H, d, J=7.2 Hz),
1.04(3H, d, J=6.9 Hz), 1.53(9H, s), 2.35(1H, m), 3.43 and 3.59(2H,
ABq, J=18.3 Hz), 3.81(3H, s), 4.45 and 4.57(2H, ABq, J=11.7 Hz),
4.84(1H, d, J=4.5 Hz), 4.99(1H, d, J=4.8 Hz), 5.21 and 5.28(2H,
ABq, J=12.0 Hz), 5.99(1H, dd, J=4.8 and 9.0 Hz), 6.91(2H, d, J=8.7
Hz), 6.98(1H, s), 7.25-7.32(10H, m), 7.35(2H, d, J=8.7 Hz),
7.92(1H, s), 7.99(1H, d, J=9.0 Hz).
[0405] IR (KBr) cm.sup.-1: 3392, 3283, 3062, 3032, 2969, 2934,
2835, 1791, 1721, 1613, 1585, 1551, 1514, 1455, 1387, 1368, 1302,
1246, 1155, 1096, 1061, 1030.
[0406] MS(ESI): 938.sup.+(M+H.sup.+).
[0407] Elemental analysis as
C.sub.44H.sub.45Cl.sub.2N.sub.5O.sub.10S.sub.- 2.multidot.0.1
CHCl.sub.3.multidot.0.4H.sub.2O-0.4 AcOEt.
[0408] Calc.: C, 55.26; H, 4.98; N, 7.05; S, 6.46; Cl, 8.21 (%).
Found: C, 55.22; H, 4.64; N, 6.90; S, 6.20; Cl, 8.37 (%).
[0409] Quarternary Ammonium Salt Ester:
[0410] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 0.87(3H, d, J=6.9 Hz),
0.89(3H, d, J=7.2 Hz), 1.36(9H, brs), 1.46(9H, s), 2.03(2H,
quintet-like), 2.15(1H, sextet-like), 2.78(3H, brs), 3.18(2H,
t-like), 3.27 and 3.43(2H, ABq, J=13.2 Hz), 3.76(3H, s), 4.43(2H,
t-like), 4.56(1H, d, J=6.0 Hz), 5.20(1H, d, J=5.4 Hz), 5.21 and
5.30(2H, ABq, J=11.7 Hz), 5.70(2H, brs), 6.00(1H, dd, J=5.4 and 8.4
Hz), 6.86(1H, s), 6.89(2H, d, J=8.7 Hz), 6.95(1H, d, J=3.3 Hz),
7.21-7.44(12H, m), 7.78(1H, dd, J=6.3 and 8.4 Hz), 8.41(1H, d,
J=3.3 Hz), 8.60(1H, d, J=6.3 Hz), 8.87(1H, d, J=8.4 Hz), 9.74(1H,
d, J=8.4 Hz), 12.1(1H, brs).
[0411] IR (KBr) cm.sup.-1: 3423, 3061, 3032, 2972, 2933, 1792,
1718, 1685, 1630, 1613, 1584, 1550, 1515, 1495, 1455, 1392, 1367,
1247, 1154, 1061, 1028.
[0412] MS(ESI): 1191.sup.+(M-I.sup.+).
EXAMPLE 14
[0413] 61
[0414] I-3k-5d:
[0415] .sup.1H-NMR (D.sub.2O) .delta.: 2.31(2H, quintet-like),
2.68(3H, s), 3.05(2H, t, J=8.1 Hz), 3.14 and 3.40 (2H, ABq, J=18.0
Hz), 3.91(2H, m), 4.53(2H, t, J=6.9 Hz), 4.69(1H, m), 5.20(1H, d,
J=4.8 Hz), 5.58 and 5.67(2H, ABq, J=14.7 Hz), 5.84(1H, d, J=4.8
Hz), 7.06(1H, d, J=3.6 Hz), 7.69(1H, dd, J=6.3 and 8.4 Hz),
8.12(1H, d, J=3.6 Hz), 8.60(1H, d, J=8.4 Hz), 8.65(1H, d, J=6.3
Hz).
[0416] IR (KBr) cm.sup.-1: 3388, 1772, 1605, 1539, 1498, 1466,
1391, 1362, 1321, 1223, 1152, 1120, 1064, 1034.
[0417] MS(ESI):693.sup.+(M+H.sup.+).
[0418] Elemental analysis as
C.sub.27H.sub.29ClN.sub.8O.sub.8S.sub.2.multi-
dot.5.62H.sub.2O.
[0419] Calc.: C, 40.82; H, 5.11; N, 14.11; Cl, 4.46; S, 8.07 (%).
Found: C, 40.41; H, 4.70; N, 14.05; Cl, 4.27; S, 8.03 (%).
[0420] 7-Side Chain
[0421] .sup.1H-NMR (d.sub.6-DMSO) .delta.: -0.03(3H, s), -0.01(3H,
s), 0.77(9H, s), 1.46(9H, s), 3.86-3.99(2H, m), 4.62(1H, t-like),
6.83(1H, s), 7.20-7.50(11H, m), 11.1 (1H, brs).
[0422] IR (KBr) cm.sup.-1:3450, 3159, 3078, 2956, 2795, 1772, 1698,
1428, 1418, 1373, 1294, 1240, 1190, 1002.
[0423] MS(ESI):690.sup.+(M+H.sup.+).
[0424] 3-Chloromethyl Compound:
[0425] .sup.1H-NMR (CDCl.sub.3) .delta.: 0.00(6H, s), 0.82(9H, s),
1.49(9H, s), 3.21 and 3.46(2H, ABq, J=18.0 Hz), 3.77(3H, s),
4.12(2H, t-like), 4.36 and 4.52(2H, ABq, J=12.0 Hz), 4.93(1H, d,
J=4.8 Hz), 5.04(1H, m), 5.16 and 5.24(2H, ABq, J=11.7 Hz), 5.93(1H,
dd, J=4.8 and 9.3 Hz), 6.85(2H, d, J=8.7 Hz), 6.89(1H, s),
7.22-7.29(10H, m), 7.32(2H, d, J=8.7 Hz), 7.61(1H, d, J=9.3 Hz),
8.22(1H, s).
[0426] IR (KBr) cm.sup.-1: 3470, 3283, 2954, 2932, 1788, 1720,
1612, 1585, 1556, 1514, 1455, 1388, 1368, 1301, 1248, 1173, 1157,
1102, 1064, 1034.
[0427] Quarternary Ammonium Salt Ester:
[0428] IR (KBr) cm.sup.-1: 3421, 3062, 3032, 2930, 2855, 1791,
1718, 1686, 1630, 1612, 1585, 1550, 1515, 1495, 1455, 1392, 1367,
1248, 1175, 1154, 1102, 1064, 1029.
[0429] MS(ESI): 1293.sup.+(M-I.sup.+).
EXAMPLE 15
[0430] 62
[0431] I-3l-5d:
[0432] .sup.1H-NMR (D.sub.2O) .delta.: 2.31(2H, quintet-like),
2.68(3H, s), 3.05(2H, t, J=8.1 Hz), 3.17 and 3.38 (2H, ABq, J=17.7
Hz), 3.94(2H, m), 4.53(2H, t, J=7.2 Hz), 4.70(1H, m), 5.18(1H, d,
J=4.8 Hz), 5.55 and 5.68(2H, ABq, J=15.0 Hz), 5.88(1H, d, J=4.8
Hz), 7.04(1H, d, J=3.3 Hz), 7.69(1H, dd, J=6.3 and 8.4 Hz),
8.12(1H, d, J=3.3 Hz), 8.60(1H, d, J=8.4 Hz), 8.64(1H, d, J=6.3
Hz).
[0433] IR (KBr) cm.sup.-1: 3398, 1774, 1603, 1538, 1498, 1466,
1392, 1362, 1320, 1064.
[0434] MS(ESI):693.sup.+(M+H.sup.+).
[0435] Elemental analysis as
C.sub.27H.sub.29ClN.sub.8O.sub.8S.sub.2.multi- dot.9.0H.sub.2O.
[0436] Calc.: C, 37.92; H, 5.54; N, 13.10; Cl, 4.15; S, 7.50 (%).
Found: C, 37.77; H, 4.42; N, 13.09; Cl, 4.24; S, 7.49 (%).
[0437] 7-Side Chain
[0438] .sup.1H-NMR (d.sub.6-DMSO) .delta.: -0.03(3H, s), -0.01(3H,
s), 0.77(9H, s), 1.46(9H, s), 3.87-3.99(2H, m), 4.63(1H, t-like),
6.83(1H, s), 7.22-7.48(11H, m), 11.1 (1H, brs).
[0439] IR (KBr) cm.sup.-1: 3450, 3159, 3078, 2955, 2794, 1772,
1697, 1428, 1417, 1373, 1294, 1240, 1191, 1002.
[0440] MS(ESI):690.sup.+(M+H.sup.+).
[0441] Quarternary Ammonium Salt Ester:
[0442] IR (KBr) cm.sup.-1: 3423, 3062, 3032, 2930, 2855, 1792,
1718, 1687, 1630, 1613, 1585, 1550, 1515, 1495, 1455, 1392, 1367,
1248, 1174, 1154, 1102, 1064, 1030.
[0443] MS(ESI): 1293.sup.+(M-I.sup.+).
EXAMPLE 16
[0444] 63
[0445] I-3f-2a:
[0446] .sup.1H-NMR (D6-dmso) .delta.: 1.39(3H, J=7.2 Hz), 2.99 and
3.44(2H, ABq, J=17.4 Hz), 4.56(1H, q, J=7.2 Hz), 4.68 and 5.16(2H,
ABq, J=13.2 Hz), 5.05(1H, d, J=4.8 Hz), 5.71(1H, dd, J=4.8, 8.4
Hz), 6.83 and 8.46(4H, A2B2q, J=6.6 Hz), 7.42(2H, s), 8.19(2H, s),
9.71(1H, d, J=8.4 Hz).
[0447] IR (KBr) cm.sup.-1: 3409, 3205, 1776, 1656, 1539, 1375,
1168, 1035, 842.
[0448] Positive ESIMS: m/z 582 [M+H]+. Negative ESIMS: m/z 580
[M-H]-.
[0449] Quaternary Salt Ester:
[0450] .sup.1H-NMR (CDCl.sub.3--CD.sub.3OD) .delta.: 1.53(9H, s),
1.56(9H, s), 1.61(3H, d, J=7.2 Hz), 3.18 and 3.75(2H, ABq, J=18.6
Hz), 3.83(3H, s), 4.99(1H, q, J=7.2 Hz), 5.09(1H, d, J=5.1 Hz),
5.21 and 5.31(2H, ABq, J=11.7 Hz), 5.27 and 5.47(2H, ABq, J=13.8
Hz), 5.94(1H, d, J=5.1 Hz), 6.90(2H, J=9 Hz), 6.91 (1H, s),
7.31-7.36(12H, m), 7.96(2H, m), 8.73(1H, d, J=6.6 Hz).
[0451] IR (KBr) cm.sup.-1: 3401, 2978, 2935, 1793, 1741, 1719,
1642, 1587, 1532, 1247, 1148, 1063, 701.
EXAMPLE 17
[0452] 64
[0453] I-3c-2a:
[0454] .sup.1H-NMR (D6-dmso) .delta.: 1.28-1.36 (4H, m), 3.03 and
3.44(2H, ABq, J=17.7 Hz), 4.72 and 5.12(2H, ABq, J=13.8 Hz),
5.05(1H, d, J=4.8 Hz), 5.71(1H, dd, J=4.8, 8.7 Hz), 6.85 and
8.40(4H, A2B2q, J=6.6 Hz), 7.45(2H, s), 8.27(2H, s), 9.71(1H,
m).
[0455] IR (KBr) cm.sup.-1: 3349, 3199, 1776, 1656, 1538, 1376,
1170, 1035, 972.
[0456] Positive ESIMS: m/z 594 [M+H]+. Negative ESIMS: m/z 592
[M-H]-.
[0457] Quaternary Salt Ester:
[0458] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.35(9H, s),
1.41-1.54(22H, m), 3.22 and 3.89(2H, ABq, J=18.3 Hz), 3.83(3H, s),
5.12(1H, d, J=5.1 Hz), 5.22 and 5.30(2H, ABq, J=11.7 Hz), 5.48 and
5.64(2H, ABq, J=8.4 Hz), 6.02(1H, dd, J=5.1, 9 Hz), 6.91 and
7.34(4H, A2B2q, J=8.4 Hz), 8.17(1H, br s), 8.38 and 8.93(4H, A2B2q,
J=7.5 Hz), 8.61(1H, d, J=9 Hz), 10.2(1H, s).
[0459] IR (KBr) cm.sup.-1: 3425, 3249, 2979, 2935, 1794, 1718,
1642, 1586, 1532, 1458, 1370, 1247, 1149, 1031, 838.
EXAMPLE 18
[0460] 65
[0461] I-3c-5d:
[0462] .sup.1H-NMR (D.sub.2O) .delta.: 1.26-1.32 (4H, m), 2.31(2H,
q like), 2.68(3H, s), 3.06(2H, t, J=8.1 Hz), 3.15 and 3.39(2H, ABq,
J=17.7 Hz), 4.54(2H, t like), 5.17(1H, d, J=4.5 Hz), 5.57 and
5.68(2H, ABq, J=15 Hz), 5.80(1H, d, J=4.5 Hz), 7.05(1H, d, J=3.3
Hz), 7.70(1H, t, J=ca7 Hz), 8.13(1H, d, J=2.4 Hz), 8.60(1H, d,
J=8.4 Hz), 8.65(1H, d, J=6 Hz).
[0463] IR (KBr) cm.sup.-1: 3398, 2820, 1773, 1608, 1540, 1395,
1225, 1033, 968, 761.
[0464] Positive ESIMS: m/z 689 [M+H]+. Negative. ESIMS: m/z 687
[M-H]-.
[0465] Quaternary Salt Ester:
[0466] .sup.1H-NMR (CDCl.sub.3) d: 1.41(9H, s), 1.46-1.52(22H, m),
2.23(2H, m), 2.92(3H, s), 3.35 and 3.78(2H, ABq, J=18 Hz), 3.38(2H,
m), 3.81(3H, s), 4.45(2H, t like), 5.20(1H, d, J=5.1 Hz), 5.24 and
5.30(2H, ABq, J=11.4 Hz), 5.76 and 5.90(2H, ABq, J=14.1 Hz),
6.02(1H, dd, J=5.1, 8.7 Hz), 6.87 and 7.33(4H, A2B2q, J=8.4 Hz),
7.01 (1H, br s), 7.64 (1H, t like), 8.02(1H, br s), 8.30(2H, m),
8.51(2H, d like), 8.61(1H, d, J=9 Hz).
[0467] IR (KBr) cm.sup.-1: 3424, 3253, 2976, 2932, 1793, 1716,
1685, 1632, 1613, 1549, 1516, 1455, 1392, 1367, 1248, 1152, 1031,
754.
[0468] 3-Cl Methyl Compound:
[0469] .sup.1H-NMR (CDCl.sub.3) d: 1.41(9H, s), 1.47-1.53(13H, m),
3.48 and 3.63(2H, ABq, J=18.3 Hz), 3.82(3H, s), 4.49(2H, s),
5.06(1H, d, J=5.1 Hz), 5.08(1H, q, J=7.2 Hz), 5.21 and 5.28(2H,
ABq, J=11.7 Hz), 5.99(1H, dd, J=5.1, 9.3 Hz), 6.91 and 7.36(4H,
A2B2q, J=8.7 Hz), 8.13(1H, br s), 8.59(1H, d, J=9.3 Hz).
[0470] IR (KBr) cm.sup.-1: 3378, 3268, 2979, 2935, 2838, 1793,
1719, 1613, 1550, 1517, 1457, 1369, 1248, 1154, 1032.
[0471] 7-Side Chain
[0472] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.40(9H, s),
1.43-1.55(13H, m).
[0473] IR (CHCl.sub.3) cm.sup.-1:3405, 2983, 2935, 1719, 1626,
1550, 1153.
EXAMPLE 19
[0474] 66
[0475] I-3b-5d:
[0476] .sup.1H-NMR (D.sub.2O) .delta.: 2.31(2H, q like, J=7.5 Hz),
2.68(3H, s), 3.04(2H, t like), 3.17 and 3.31(2H, ABq, J=17.7 Hz),
4.53(2H, t like), 5.10(1H, d, J=2.1 Hz), 5.12(1H, d, J=4.5 Hz),
5.27(1H, d, J=2.1 Hz), 5.51 and 5.76(2H, ABq, J=15 Hz), 5.88(1H, d,
J=4.5 Hz), 6.99(1H, d, J=3.6), 7.67(1H, dd, J=6.4, 8.1 Hz),
8.12(1H, d, J=3.6 Hz), 8.59(1H, d, J=8.1 Hz), 8.63(1H, d, J=6.4
Hz).IR (KBr) cm.sup.-1: 3398, 1774, 1606, 1539, 1498, 1468, 1392,
1203, 759.
[0477] Positive ESIMS: m/z 675 [M+H]+.
[0478] Elemental analysis as
C.sub.27H.sub.27N.sub.8O.sub.7S.sub.2Cl.multi- dot.5.5H.sub.2O.
[0479] Calc.: C, 41.89; H, 4.95; N, 14.47; S, 8.28; Cl, 4.58 (%).
Found: C, 41.92; H, 4.72; N, 14.49; S, 8.38; Cl, 4.66 (%).
[0480] Quaternary Salt Ester:
[0481] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.48(9H, s), 1.53(9H, s),
2.20(2H, m), 2.90(3H, s) 3.19 and 3.64(2H, ABq, J=18 Hz), 3.36(2H,
t like), 3.78(3H, s), 4.42(2H, t like), 4.95(1H, d, J=4.8 Hz), 5.20
and 5.28(2H, ABq, J=11.7 Hz), 5.59(1H, d, J=1.5 Hz), 5.75(1H, d,
J=1.5 Hz), 5.84(1H, dd, J=4.8, 8.6 Hz), 6.83 (2H, d, J=8.7 HZ),
6.89(1H, s), 7.04(1H, br s), 7.23-7.36 (12H, m), 7.62(1H, m),
8.20(1H, m), 8.46(1H, d, J=9.3 Hz), 8.56(1H, d, J=6.0 Hz), 8.65(1H,
m).
[0482] IR (CHCl.sub.3) cm.sup.-1: 3403, 1793, 1720, 1685, 1632,
1613, 1551, 1517, 1154.
[0483] 3-Chloromethyl Compound:
[0484] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.53(9H, s), 3.23 and
3.43(2H, ABq, J=18 Hz), 3.80(3H, s), 4.36 and 4.55(2H, ABq, J=12
Hz), 4.75(1H, d, J=5.1 Hz), 5.16 and 5.25(2H, ABq, J=11.4 Hz),
5.61(1H, d, J=1.8), 5.81(1H, d, J=1.8), 5.88(1H, dd, J=5.1, 9.0
Hz), 6.87-6.92 (3H, m), 7.16-7.39 (12H, m), 8.56(1H,br s).
[0485] IR (CHCl.sub.3) cm.sup.-1: 3403, 1793, 1725, 1613, 1550,
1517, 1248, 1215, 1155.
[0486] 7-Side Chain:
[0487] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.48(9H, s), 5.65(1H, d,
J=2.4), 5.75(1H, d, J=2.4), 6.93(1H, s), 7.27-7.34(10H, m).
[0488] Positive FABMS(Matrix:m-NBA): m/z 558[M+H]+, 580[M+Na]+,
1115[2M+H]+. Negative FABMS(Matrix:m-NBA): m/z 556[M-H]-, 1113[2M
H]-.
[0489] IR (CHCl.sub.3) cm.sup.-1: 3602, 3404, 1723, 1603, 1550,
1285, 1253, 1227, 1155.
EXAMPLE 20
[0490] 67
[0491] I-4d-5d:
[0492] .sup.1H-NMR (D.sub.2O) .delta.: 1.47 (6H, s), 2.30(2H, q
like), 2.68(3H, s), 3.06(2H, t, J=8 Hz), 3.18 and 3.39(2H, ABq,
J=17.7 Hz), 4.52(2H, t like), 5.18(1H, d, J=4.8 Hz), 5.56 and
5.68(2H, ABq, J=15 Hz), 5.82(1H, d, J=4.8 Hz), 7.04(1H, d, J=3.3
Hz), 7.68(1H, t like), 8.12(1H, d, J=3.6 Hz), 8.58(1H, d, J=8.1
Hz), 8.64(1H, d, J=6 Hz).
[0493] IR (KBr) cm.sup.-1: 3405, 1772, 1608, 1535, 1394, 1362,
1160, 790, 760.
[0494] Positive ESIMS: m/z 735 [M+H]+. Negative ESIMS: m/z 733
[M-H]-.
[0495] Elemental analysis
C.sub.28H.sub.31N.sub.8O.sub.7S.sub.2Br.multidot- .5H.sub.2O
.iota..tau..
[0496] Calc.: C, 40.73; H, 5.00; N, 13.57; S, 7.77; Br, 9.68 (%).
Found: C, 40.67; H, 4.91; N, 13.39; S, 7.50; Br, 9.64 (%).
[0497] Quaternary Salt Ester:
[0498] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.43(9H, s), 1.48(9H, s),
1.51(3H, s), 1.59(3H, s), 2.22(2H, m), 2.91(3H, s), 3.37(2H, t
like), 3.31 and 3.80(2H, ABq, J=18.6 Hz), 3.82(3H, s), 4.45(2H, t
like), 5.19(1H, d, J=5.4 Hz), 5.23 and 5.30(2H, ABq, J=11.4 Hz),
5.64 and 5.79(2H, ABq, J=15 Hz), 6.07(1H, dd, J=5.4, 9 Hz), 6.87
and 7.33(4H, A2B2q, J=8.7 Hz), 7.04 (1H, br s), 7.67(1H, t like),
8.06 (1H, d, J=9 Hz), 8.26(1H, br s), 8.39(1H, br s), 8.52(1H, d,
J=9 Hz), 8.58(1H, d, J=6 Hz).
[0499] 3-Chloromethyl Compound:
[0500] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.43(9H, s), 1.52(9H, s),
1.62(6H, s), 3.48 and 3.65(2H, ABq, J=18.3 Hz), 3.82(3H, s), 4.44
and 4.55(2H, ABq, J=12 Hz), 5.04(1H, d, J=4.8 Hz), 5.19 and
5.27(2H, ABq, J=12 Hz), 6.03(1H, dd, J=5.1, 9 Hz), 6.91 and
7.35(4H, A2B2q, J=8.7 Hz), 8.02(1H,d, J=9 Hz), 8.17(1H, br s).
[0501] IR (KBr) cm.sup.-1: 3280, 2980, 2935, 2837, 1789, 1720,
1614, 1549, 1516, 1369, 1248, 1155.
[0502] 7-Side Chain:
[0503] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.48(9H, s), 1.49(9H, s),
1.53(3H, s), 1.56(3H, s).
[0504] IR (CHCl.sub.3) cm.sup.-1: 3406, 3019, 2983, 2937, 1724,
1544, 1369, 1226, 1151.
[0505] Positive ESIMS: m/z 508[M+H]+, m/z 530[M+Na]+.
[0506] Negative ESIMS: m/z 506[M-H]-, m/z 528[M+Na-2H]-
[0507] The other example compounds are shown below.
EXAMPLE 22
[0508] 68
[0509] .sup.1H-NMR (D.sub.2O) .delta.: 2.31(2H, m), 2.59(2H, t,
J=6.9 Hz), 2.69(3H, s), 3.06(2H, m), 3.21 and 3.35 (2H, ABq, J=17.7
Hz), 4.39(2H, m), 4.53(2H, t, J=6.9 Hz), 5.14(1H, d, J=5.1 Hz),
5.54 and 5.71(2H, ABq, J=15.0 Hz), 5.76(1H, d, J=5.1 Hz), 7.03(1H,
d, J=3.3 Hz), 7.69(1H, dd, J=6.3 and 8.4 Hz), 8.13(1H, d, J=3.3
Hz), 8.60(1H, d, J=8.4 Hz), 8.66(1H, d, J=6.3 Hz).
[0510] IR (KBr) cm.sup.-1: 3397, 3132, 2458, 1775, 1615, 1540,
1499, 1466, 1389, 1223, 1164, 1122, 1063, 1027.
[0511] MS(ESI):677.sup.+(M+H.sup.+).
[0512] Elemental analysis as
C.sub.27H.sub.29ClN.sub.8O.sub.7S.sub.2 2.8H.sub.2O.
[0513] Calc.: C, 44.57; H, 4.79; N, 15.40; Cl, 4.87; S, 8.81 (%).
Found: C, 44.51; H, 4.57; N, 15.37; Cl, 4.81; S, 8.66 (%).
[0514] 3-Chloromethyl Compound:
[0515] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.52(9H, s), 2.89(2H, m),
3.28 and 3.53(2H, ABq, J=18.3 Hz), 3.81(3H, s), 4.22 and 4.54(2H,
ABq, J=12.0 Hz), 4.59(3H, t, J=6.6 Hz), 4.95(1H, d, J=4.8 Hz), 5.17
and 5.26(2H, ABq, J=11.7 Hz), 5.90(1H, dd, J=4.8 and 8.7 Hz),
6.84(1H, s), 6.90(2H, d, J=9.0 Hz), 7.24-7.38(12H, m), 7.48(1H, d,
J=8.7 Hz), 8.50(1H, brs).
[0516] IR (KBr) cm.sup.-1: 3283, 3062, 3031, 2978, 2836, 1789,
1721, 1613, 1549, 1515, 1454, 1386, 1369, 1302, 1246, 1158, 1096,
1063, 1031.
[0517] MS(ESI): 910.sup.+(M+H.sup.+).
[0518] Elemental analysis as
C.sub.42H.sub.41Cl.sub.2N.sub.5O.sub.10S.sub.- 2.multidot.0.3
CHCl.sub.3.multidot.0.7H.sub.2O.
[0519] Calc.: C, 52.96; H, 4.49; N, 7.30; S, 6.69; Cl, 10.72 (%).
Found: C, 52.91; H, 4.34; N, 7.33; S, 6.64; Cl, 10.74 (%).
[0520] Quaternary Salt Ester:
[0521] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37(9H, s), 1.46(9H,
s), 2.03(2H, m), 2.77(3H, brs), 2.87(2H, t, J=6.6 Hz), 3.18(2H, t,
J=6.6 Hz), 3.28 and 3.35(2H, m), 3.75(3H, s), 4.36(2H, t, J=6.3
Hz), 4.43(2H, t, J=6.6 Hz), 5.15(1H, d, J=4.8 Hz), 5.21 and
5.29(2H, ABq, J=11.7 Hz), 5.66 and 5.72(2H, ABq, J=15.0 Hz),
5.94(1H, dd, J=4.8 and 9.0 Hz), 6.75(1H, s), 6.88(2H, d, J=8.7 Hz),
6.99(1H, d, J=3.3 Hz), 7.20-7.40(12H, m), 7.78(1H, dd, J=6.0 and
8.1 Hz), 8.43(1H, d, J=3.3 Hz), 8.59(1H, d, J=6.0 Hz), 8.88(1H, d,
J=8.1 Hz), 9.72(1H, d, J=9.0 Hz), 12.1(1H, brs).
[0522] IR (KBr) cm.sup.-1: 3424, 3061, 3031, 2975, 2934, 1791,
1719, 1685, 1630, 1613, 1548, 1515, 1495, 1455, 1392, 1367, 1247,
1156, 1029.
[0523] MS(ESI):
1163.sup.+(C.sub.58H.sub.64ClN.sub.8O.sub.12S.sub.2.sup.+)- .
EXAMPLE 23
[0524] 69
[0525] .sup.1H-NMR (D.sub.2O) .delta.: 1.90(2H, m), 2.31(4H, m),
2.44(2H, m), 2.68(3H, s), 3.05(2H, t, J=8.1 Hz), 3.17 and 3.39 (2H,
ABq, J=18.0 Hz), 4.54(2H, t, J=6.9 Hz), 5.20(1H, d, J=4.8 Hz), 5.56
and 5.69(2H, ABq, J=15.0 Hz), 5.83(1H, d, J=4.8 Hz), 7.04(1H, d,
J=3.3 Hz), 7.69(1H, dd, J=6.3 and 8.4 Hz), 8.12(1H, d, J=3.3 Hz),
8.60(1H, d, J=8.4 Hz), 8.64(1H, d, J=6.3 Hz).
[0526] IR (KBr) cm.sup.-1: 3398, 2948, 1774, 1610, 1538, 1498,
1458, 1392, 1287, 1236, 1158, 1120, 1064, 1032.
[0527] MS(ESI): 703.sup.+(M+H.sup.+).
[0528] Elemental analysis as
C.sub.29H.sub.31ClN.sub.8O.sub.7S.sub.2.multi- dot.6.5H.sub.2O.
[0529] Calc.: C, 42.46; H, 5.41; N, 13.66; Cl, 4.32; S, 7.82 (%).
Found: C, 42.34; H, 4.87; N, 13.71; Cl, 4.39; S, 7.79 (%).
[0530] 7-Side Chain
[0531] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.47(9H, s),
1.75-2.00(2H, m), 2.20-2.38(2H, m), 2.44-2.54(2H, m), 6.82(1H, s),
7.1-7.5(10H, m), 12.0(1H, brs).
[0532] IR (KBr) cm.sup.-1: 3209, 3064, 3031, 2980, 2955, 1719,
1619, 1554, 1495, 1454, 1394, 1370, 1295, 1249, 1204, 1155, 1067,
1037.
[0533] MS(ESI):586.sup.+(M+H.sup.+).
[0534] Elemental analysis as
C.sub.28H.sub.30ClN.sub.8O.sub.7S.sub.1.multi- dot.1.3H.sub.2O.
[0535] Calc.: C, 55.18; H, 5.06; N, 6.89; Cl, 5.82; S, 5.26 (%).
Found: C, 55.17; H, 4.92; N, 7.28; Cl, 5.65; S, 5.24 (%).
[0536] 3-Chloromethyl Compound:
[0537] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.53(9H, s), 2.05-2.18(2H,
m), 2.47-2.78(4H, m), 3.26 and 3.51(2H, ABq, J=18.3 Hz), 3.82(3H,
s), 4.40 and 4.56(2H, ABq, J=12.0 Hz), 4.96(1H, d, J=4.8 Hz),
5.24(1H, d, J=5.1 Hz), 5.21 and 5.27(2H, ABq, J=12.0 Hz), 5.97(1H,
dd, J=5.1 and 9.6 Hz), 6.90(2H, d, J=8.7 Hz), 6.92(1H, s),
7.25-7.31(10H, m), 7.35(2H, d, J=8.7 Hz), 7.44(1H, d, J=9.6 Hz),
8.00(1H, s).
[0538] IR (KBr) cm.sup.-1: 3378, 3285, 3063, 3031, 2978, 2836,
1790, 1722, 1613, 1585, 1549, 1515, 1454, 1385, 1368, 1300, 1247,
1203, 1156, 1112, 1098, 1063, 1034.
[0539] MS(ESI):936.sup.+(M+H.sup.+).
[0540] Quarternary Ammonium Salt Ester:
[0541] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.36(9H, brs), 1.46(9H,
s), 1.79-2.09(2H, m), 2.03(2H, quintet-like), 2.30-2.61(4H, m),
2.77(3H, brs), 3.17(2H, t-like), 3.30 and 3.42(2H, ABq, J=13.2 Hz),
3.76(3H, s), 4.43(2H, t-like), 5.21(1H, d, J=4.8 Hz), 5.22 and
5.31(2H, ABq, J=11.7 Hz), 5.71(2H, brs), 6.01(1H, dd, J=4.8 and 8.7
Hz), 6.82(1H, s), 6.90(2H, d, J=8.4 Hz), 6.96(1H, d, J=3.3 Hz),
7.21-7.44(12H, m), 7.78(1H, dd, J=6.3 and 8.1 Hz), 8.42(1H, d,
J=3.3 Hz), 8.63(1H, d, J=6.3 Hz), 8.88(1H, d, J=8.1 Hz), 9.77(1H,
d, J=8.7 Hz), 12.1(1H, brs).
[0542] IR (KBr) cm.sup.-1: 3424, 3061, 2975, 1791, 1718, 1685,
1630, 1613, 1584, 1550, 1515, 1495, 1455, 1392, 1367, 1298, 1248,
1155, 1123, 1065, 1030, 1018.
EXAMPLE 24
[0543] 70
[0544] .sup.1H-NMR (D.sub.2O) .delta.: 1.50 (6H, br s), 2.30(2H, q
like), 2.69(3H, s), 3.06(2H, t, J=7.8 Hz), 3.38 and 3.63(2H, ABq,
J=18.3 Hz), 4.52(2H, m), 4.98(1H, d, J=4.8 Hz), 5.63 and 5.75(2H,
ABq, J=15.3 Hz), 6.05(1H, d, J=4.8 Hz), 7.06(1H, d, J=3.3 Hz),
7.69(1H, dd, J=6.0, 8.1 Hz), 8.13(1H, d, J=3.3 Hz), 8.59(1H, d,
J=8.1 Hz), 8.67(1H, d, J=6.0 Hz).
[0545] IR (KBr) cm.sup.-1: 3412, 1784, 1618, 1535, 1396, 1361,
1159, 858, 760.
[0546] Elemental analysis as
C.sub.28H.sub.31N.sub.8O.sub.8S.sub.2Br.multi- dot.6.4H.sub.2O
[0547] Calc.: C, 38.79; H, 5.09; N, 12.93; S, 7.40; Br, 9.22 (%).
Found: C, 38.82; H, 4.85; N, 12.90; S, 7.43; Br, 9.02 (%).
[0548] Quarternary Ammonium Salt Ester (S-Oxide):
[0549] IR (KBr) cm.sup.-1: 3427, 2978, 2935, 1802, 1722, 1687,
1549, 1516, 1458, 1390, 1367, 1250, 1153, 1030, 766.
[0550] 3-Chloromethyl Compound (S-Oxide):
[0551] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.42(9H, s), 1.52(9H, s),
1.61(6H, br s), 3.43 and 3.82(2H, ABq, J=18.6 Hz), 3.82(3H, s),
4.24 and 5.03(2H, ABq, J=12.6 Hz), 4.59(1H, dd, J=1.2, 5.1 Hz),
5.24 and 5.30(2H, ABq, J=12 Hz), 6.19(1H, dd, J=5.1, 9.6 Hz), 6.92
and 7.37(4H, A2B2q, J=6.6 Hz), 7.94(1H,d, J=10.2 Hz), 8.37(1H, br
s).
EXAMPLE 25
[0552] 71
[0553] (1) To a solution of compound 17 (4.85 g) in THF 38 ml, were
added triphenylphosphine (5.71 g) and hydroxyphtalimide (3.55 g)
and the mixture was stirred under ice-cooling. Diisopropyl
azodicarbonate (4.3 ml) was added dropwise and the mixture was
allowed to stand at 4.degree. C. overnight. The mixture was
concentrated in vacuum, purified with silica gel chromato, and
crystallized from eter/hexane to give compound 18 (7.6 g).
[0554] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.67(3H, d, J=7.2 Hz),
5.05(1H, q, J=7.2 Hz), 6.93 (1H, s), 7.22-7.32(10H, m),
7.70-7.79(4H, m).
[0555] IR (KBr) cm.sup.-1: 1791, 1736, 1284, 700.
[0556] FABMS: m/z 402 [M+H]+, 803 [2M+H]+. 72
[0557] (2) To a solution of compound 18 (4.82 g) in
CH.sub.2Cl.sub.2 12 ml, was added at -25.degree. C. methyl
hydrazine 0.63 ml and the mixture was stirred for 1.5 hr. The
obtained crystal was collected by filtration and the filtrate was
diluted with MeOH 25 ml. Carboxylic acid 9 (3.7 g) was added under
ice-cooling and the mixture was stirred for 2 hr and allowed to
stand at 4.degree. C. overnight. The reaction solution was
concentrated in vacuum and dissolved to AcOEt, which was washed
with NaHCO.sub.3 water, hydrochloric acid water, and saline, then
dried over MgSO.sub.4 and evaporated to give compound 4-3 (4.74
g).
[0558] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.46(3H, d, J=6.9H),
1.47(9H, s), 5.00(1H, q, J=6.9 Hz), 6.85(1H, s), 7.26-7.42(10H, m),
12.06(1H, s).
[0559] IR (KBr) cm.sup.-1: 3422, 3193, 3062, 3032, 2983, 1740,
1719, 1602, 1554, 1453, 1370, 1250, 1155, 1096, 1038, 967, 744,
699.
[0560] FABMS: m/z 560 [M+H]+, 1119 [2M+H]+.
[0561] (3) To a solution of carboxylic acid 4-3 (3.50 g, 6.25 mmol)
and ACLE.multidot.HCl 10 (2.53 g 6.25 mmol) in CH.sub.2Cl.sub.2 21
ml, were added WSCD.multidot.HCl (1.20 g 1 eq) and Pyridine (0.51
ml, 1.0 eq) under ice-cooling, and the mixture was stirred at the
same temperature for 1 hr. The reaction solution was washed with
brine, dried with anhydrous MgSO.sub.4, concentrated in vacuum, and
purified with silica gel chromato to give a foam-like residue 11-3
(4.60 g).
[0562] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.53(9H, s), 1.64(3H, d,
J=7.2 Hz), 3.39 and 3.58(2H, ABq, J=18.3 Hz), 3.81(3H, s), 4.42 and
4.59(2H, ABq, J=12 Hz), 4.97(1H, d, J=5.1 Hz), 5.08(1H, q, J=7.2
Hz), 5.20 and 5.27(2H, ABq, J=11.7 Hz), 6.01(1H, dd, J=5.1, 9.3
Hz), 6.88-6.91(3H, m), 7.06-7.35(12H, m), 7.85(1H, d, J=9.3 Hz),
8.15(1H, br s).
[0563] IR (KBr) cm.sup.-1: 3281, 2980, 2935, 2836, 1790, 1719,
1612, 1552, 1515, 1454, 1369, 1247, 1155, 1035, 700.
[0564] FABMS: m/z 910 [M+H]+. 73
[0565] (4) To a solution of Cl-compound 11-3 (4.60 g, 5.05 mmol) in
THF cooled to 13.degree. C., was added NaI (2.65 g 3.5 eq) and the
mixture was stirred for 30 min. The reaction solution was poured to
Na.sub.2S.sub.2O.sub.3 aq. -EtOAc and the organic layer was
separated, washed with brine, dried with anhydrous MgSO.sub.4,
concentrated in vacuum to give a foam-like residue 20 (5.07 g).
[0566] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.53(9H, s), 1.65(3H, d,
J=7.2 Hz), 3.39 and 3.67(2H, ABq, J=17.7 Hz), 3.81(3H, s), 4.33 and
4.45(2H, ABq, J=9.3 Hz), 4.96(1H, d, J=5.1 Hz), 5.08(1H, q, J=7.2
Hz), 5.20 and 5.28(2H, ABq, J=11.7 Hz), 5.95(1H, dd, J=5.1, 9.0
Hz), 6.88-6.92(3H, m), 7.23-7.39(12H, m), 7.78(1H, d, J=9.0 Hz),
8.01(1H, br s).
[0567] IR (KBr) cm.sup.-1: 3383, 3284, 2980, 2836, 1790, 1719,
1613, 1551, 1516, 1369, 1246, 1153, 1037, 700.
[0568] ABMS: m/z 1002 [M+H]+.
[0569] (5) To a solution of a material for 3-side chain, 13 (174
mg, 0.60 mmol) in MeCN 1 ml, was added iode compound 20 (570 mg,
0.60 mmol) under ice-cooling, and the mixture was stirred at the
same temperature for 3 hr and at room temperature for 2 hr. A
mixture of Toluene/Et.sub.2O/n-Hexane (1:30:30) was added dropwise
thereto and the precipitated powder was collected by filtration to
give quaternary salt 14-3a (675 mg).
[0570] .sup.1H-NMR (CDCl.sub.3) .delta.: 1.46(9H, s), 1.51(9H, s),
1.61(3H, d, J=7.2 Hz), 2.21(2H, m), 2.88(3H, s), 3.19 and 3.89(2H,
ABq, J=18.9 Hz), 3.33(2H, m), 3.80(3H, s), 4.42(2H, t like),
5.04-5.15(4H, m), 5.22 and 5.30(2H, ABq, J=12 Hz), 5.84 and
5.75(2H, ABq, J=14.7 Hz), 5.98(1H, dd, J=5.1, 8.7 Hz), 6.89(3H,m),
7.25-7.36(12H, m), 7.54(1H, t like), 7.75(H, d, J=7.8 Hz), 8.25(1H,
m), 8.56(1H, d, J=8.7 Hz), 8.95(1H, d, J=5.7 Hz).
[0571] IR (KBr) cm.sup.-1: 3423, 2976, 2932, 1792, 1718, 1687,
1613, 1550, 1515, 1496, 1454, 1367, 1248 1154, 759, 701. 74
[0572] (6) To a solution of Cl-compound 11-3 (2.13 g, 2.33 mmol) in
CH.sub.2Cl.sub.2 10 ml, was added dropwise a solution of m-CPBA
(purity:>65%, 495 mg 0.81 eq) in CH.sub.2Cl.sub.2 8 ml at
-50.degree. C. and the mixture was stirred at the same temperature
for 30 min. 5% Na.sub.2S.sub.2O.sub.3 aq. was added thereto and the
organic layer was washed with NaHCO.sub.3 aq. and brine, dried over
anhydrous MgSO.sub.4, then concentrated in vacuum. To the obtained
foam-like residue was added Et.sub.2O/n-Hexane to give oxide 15
(about 2 g) as powder.
[0573] .sup.1H-NMR (CDCl3) .delta.: 1.53(9H, s), 1.64(3H, d, J=7.2
Hz), 3.29 and 3.70(2H, ABq, J=18.6 Hz), 3.81(3H, s), 4.23 and
4.99(2H, ABq, J=12.6 Hz), 4.44(1H, d, J=5.1 Hz), 5.10(1H, q, J=7.2
Hz), 5.26 (2H, m), 6.16(1H, dd, J=5.1, 9.6 Hz), 6.88-6.94(3H, m),
7.25-7.375(12H, m), 7:90(1H, d, J=9.6 Hz), 8.32(1H, br s).
[0574] IR (KBr) cm.sup.-1: 3425, 2979, 2937, 1804, 1720, 1613,
1553, 1516, 1454, 1369, 1249 1155, 1037, 701.
[0575] (7-1) To a solution of a material for 3-side chain, 13 (324
mg 1.1 eq), in DMF 1.8 ml, were added oxide 15 (1.22 g, 1.31 mmol)
and NaBr (271 mg 2 eq) and the mixture was stirred in nitrogen
atomosphere at room temperature for 1.5 hr. DMF 2 ml and KI 1.28 g
were added thereto and the mixture was cooled to -40.degree. C., to
which was added dropwise AcCl 0.40 ml and the mixture was stirred
at -10.degree. C. for 3 hr. The reaction solution was poured to a
phosphate buffer of pH 6 containing NaCl and
Na.sub.2S.sub.2O.sub.3, then the precipitates were collected by
filtration, dissolved to acetone, and concentrated in vacuum. To
the residue was added Et.sub.2O/n-Hexane to give quaternary salt
14-3 (1.77 g).
[0576] .sup.1H-NMR (CDCl3) .delta.: 1.48(9H, s), 1.51(9H, s),
1.62(3H, d, J=7.2 Hz), 2.21(2H, m), 2.91(3H, s), 3.24 and 3.82(2H,
ABq, J=18.9 Hz), 3.36(2H, m), 3.81(3H, s), 4.43(2H, t like),
5.09(1H, q, J=7.2 Hz), 5.16(1H, d, J=5.1 Hz), 5.24 and 5.31(2H,
ABq, J=11.7 Hz), 5.58 and 5.75(2H, ABq, J=14.7 Hz), 5.99(1H, dd,
J=5.1, 8.7 Hz), 6.86(1H, s), 6.87(2H, d, J=8.7 Hz), 7.00(1H, br s),
7.24-7.38(12H, m), 7.55(1H, t like), 7.78(H, d, J=8.7 Hz), 8.25(1H,
br s), 8.47(1H, d, J=10.2 Hz), 8.50(1H, d, J=6 Hz).
[0577] IR (KBr) cm.sup.-1: 3423, 2976, 2932, 1792, 1718, 1687,
1613, 1248 1154, 759, 701.
[0578] (7-2) To a solution of a material for 3-side chain, 13 (174
mg, 0.60 mmol) in MeCN 1 ml, was added iode compound 20 (570 mg,
0.60 mmol as reduced purity) under ice-cooling and the mixture was
stirred at the same temperature for 3 hr and at room temperature
for 2 hr. A mixture of Toluene/Et.sub.2O/n-Hexane (1:30:30) was
added dropwise thereto and the precipitated powder was collected by
filtration to give quaternary salt 14-3a 675 mg.
[0579] (8) To a solution of quaternary salt 14-3 (about 1.3 mmol)
in CH.sub.2Cl.sub.2-- MeNO.sub.2 30 ml and anisole 1.7 ml, was
added an AlCl.sub.3.MeNO.sub.2 solution (1.5M, 7 ml) in nitrogen
atomosphere under ice-cooling and the mixture was stirred for 1 hr.
Ice, 1N HCl--CH.sub.3CN and Et.sub.2O were added thereto and the
water layer was separated, concentrated in vacuum, and subjected to
HP-20 chromato. The collected eluate was lyophilized to give
compound 16-3 (450 mg) as powder.
[0580] .sup.1H-NMR (D2O) .delta.: 1.43 (3H, d, J=7.2 Hz), 2.31(2H,
q like), 2.68(3H, s), 3.05(2H, t, J=8 Hz), 3.18 and 3.37(2H, ABq,
J=18 Hz), 4.53(2H, t like), 4.65 (1H, q, J=7.2 Hz), 5.17(1H, d,
J=4.8 Hz), 5.54 and 5.70(2H, ABq, J=15 Hz), 5.86(1H, d, J=4.5 Hz),
7.03(1H, d, J=3.6 Hz), 7.69(1H, dd, J=6, 8.4 Hz), 8.13(1H, d, J=3.6
Hz), 8.60(1H, d, J=8.4 Hz), 8.64(1H, d, J=6 Hz).
[0581] IR (KBr) cm.sup.-1: 3398, 1775, 1603, 1541, 1392, 1363,
1320, 1286, 1033, 762.
[0582] Positive ESIMS: m/z 677 [M+H]+. Negative ESIMS: m/z 675
[M-H]-.
[0583] Elemental analysis as
C.sub.27H.sub.29N.sub.8O.sub.7S.sub.2Cl.multi- dot.6.2H.sub.2O
[0584] Calc.: C, 41.11; H, 5.29; N, 14.20; S, 8.13; Cl, 4.49 (%).
Found: C, 40.88; H, 4.88; N, 14.23; S, 8.05; Cl, 4.57 (%).
EXAMPLE 26
[0585] 75
[0586] .sup.1H-NMR (D.sub.2O) .delta.: 1.51 (3H, d, J=7.25 Hz),
3.22 and 3.64 (Abq, J=17.9 Hz), 4.83 (1H, q, J=7.2 Hz), 5.28 (1H,
d, J=4.8 Hz), 5.35 and 5.58 (2H, ABq, J=14.6 Hz), 5.90 (1H, d,
J=4.8 Hz), 8.09 (2H, t-like), 8.57 (2H, t, J=7.8 Hz), 8.95 (2H, d,
J=5.7 Hz).
[0587] IR (KBr) cm.sup.-1: 3410, 3060, 1780, 1674, 1627, 1538,
1481, 1445, 1389, 1341, 1219, 1186, 1153, 1100, 1035.
[0588] MS(ESI): 567.sup.+(M+H).sup.+.
[0589] Elementary Analysis as
C.sub.21H.sub.19ClN.sub.6O.sub.7S.sub.2.mult- idot.2.9H.sub.2O.
[0590] Calculated: C, 40.73; H, 4.04; N, 13.57; Cl, 5.73; S, 10.36
(%). Found: C, 40.67; H, 3.87; N, 13.45; Cl, 5.50; S, 10.36
(%).
EXAMPLE 27
[0591] 76
[0592] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.36 (3H, d, J=7.1 Hz),
2.97 and 3.25 (2H, Abq, J=17.3 Hz), 4.03 (3H, s), 4.55 (1H, q,
J=7.1 Hz), 4.97 (1H, d, J=5.1 Hz), 5.61-5.72 (3H, m), 5.60 and 5.73
(2H, ABq, J=15.2 Hz), 7.37 (1H, d, J=3.3 Hz), 7.41 (1H, s), 7.78
(1H, dd, J=6.3, 8.2 Hz), 8.28 (1H, d, J=3.3 Hz), 8.74 (1H, d,
J=8.2), 9.16 (1H, d, J=6.3 Hz), 9.61 (1H, brs).
[0593] IR (KBr) cm.sup.-1:3423, 2986, 1778, 1674, 1618, 1538, 1500,
1469, 1416, 1368, 1324, 1281, 1222, 1187, 1154, 1094, 1062,
1032.
[0594] MS(ESI): 620.sup.+(M+H).sup.+.
[0595] Elementary Analysis as
C.sub.24H.sub.22ClN.sub.7O.sub.7S.sub.2.mult- idot.2.6H.sub.2O.
[0596] Calculated: C, 43.22; H, 4.11; N, 14.70; Cl, 5.32; S, 9.62
(%). Found: C, 43.16; H, 3.99; N, 14.88; Cl, 5.12; S, 9.61 (%).
EXAMPLE 28
[0597] 77
[0598] .sup.1H-NMR (D.sub.2O) .delta.: 1.50 (3H, d, J=6.9 Hz), 3.20
and 3.58 (2H, ABq, J=17.7 Hz), 4.80 and 4.84 (2H, ABq, J=6.9 Hz),
5.24 (1H, d, J=4.8 Hz), 5.37 and 5.42 (2H, ABq, J=16.2 Hz), 5.87
(1H, d, J=4.8 Hz), 7.90 (1H, dd, J=4.5, 9.4 Hz), 8.25 (1H, d, J=2.3
Hz), 8.44 (1H, d, J=2.3 Hz), 8.66 (1H, d, J=9.4 Hz), 8.94 (1H, dd,
J=1.5, 4.5 Hz).
[0599] IR (KBr) cm.sup.-1: 3416, 3136, 2939, 1776, 1674, 1625,
1535, 1447, 1383, 1346, 1317, 1232, 1185, 1155, 1100, 1066,
1035.
[0600] MS(FAB): 607.sup.+(M+H).sup.+.
[0601] Elementary Analysis as
C.sub.22H.sub.19ClN.sub.8O.sub.7S.sub.2.mult- idot.2.8H.sub.2O.
[0602] Calculated: C, 40.19; H, 3.77; N, 17.04; Cl, 5.39; S, 9.75
(%). Found: C, 40.10; H, 3.56; N, 17.01; Cl, 5.20; S, 9.73 (%).
EXAMPLE 29
[0603] 78
[0604] .sup.1H-NMR (D.sub.2O) .delta.: 1.55 (3H, d, J=7.2 Hz), 2.22
(4H, brs), 2.99 (3H, s), 3.46 and 3.92 (2H, ABq, J=17.0 Hz), 3.53
(4H, m), 3.99 and 4.74 (2H, ABq, J=13.79 Hz), 4.85 (1H, q, J=7.2
Hz), 5.36 (1H, d, J=5.1 Hz), 5.90 (1H, d, J=5.1 Hz).
[0605] IR (KBr) cm.sup.-1: 3416, 1780, 1676, 1616, 1538, 1459,
1345, 1285, 1236, 1180, 1097, 1068, 1036.
[0606] MS(FAB): 573.sup.+(M+H).sup.+.
[0607] Elementary Analysis as
C.sub.21H.sub.25ClN.sub.6O.sub.7S.sub.2.mult- idot.4.0H.sub.2O.
[0608] Calculated: C, 39.10; H, 5.16; N, 13.03; Cl, 5.50; S, 9.94
(%). Found: C, 38.86; H, 4.64; N, 13.00; Cl, 5.30; S, 9.90 (%).
EXAMPLE 30
[0609] 79
[0610] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=7.1 Hz),
3.15 and 3.50 (ABq, J=17.6 Hz), 4.54 (1H, q, J=7.1 Hz), 4.96 and
5.58 (2H, ABq, J=13.4 Hz), 5.11 (1H, d, J=4.9 Hz), 5.73 (1H, dd,
J=4.9, 8.9 Hz), 7.41 (2H,s), 7.52 (1H, d, J=6.6 Hz), 8.70 (2H, d,
J=6.6 Hz), 9.14 (1H, s), 9.75 (1H, brs).
[0611] IR (KBr) cm.sup.-1: 3414, 3086, 1738, 1661, 1620, 1527,
1446, 1390, 1351, 1307, 1210, 1118, 1066, 1036.
[0612] MS(ESI): 623.sup.+(M+H).sup.+.
[0613] Elementary Analysis as
C.sub.22H.sub.19ClN.sub.8O.sub.8S.sub.2.mult- idot.3.7H.sub.2O.
[0614] Calculated: C, 38.31; H, 3.86; N, 16.25; Cl, 5.14; S, 9.30
(%). Found: C, 38.18; H, 3.51; N, 16.22; Cl, 4.85; S, 9.24 (%).
EXAMPLE 31
[0615] 80
[0616] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.36 (3H, d, J=7.1 Hz),
3.03 and 3.32 (ABq, J=17.6 Hz), 4.29 (3H, s), 4.55 (1H, q, J=7.1
Hz), 5.00 (1H, d, J=5.0 Hz), 5.69 (1H, dd, J=5.0, 8.6 Hz), 5.75 and
5.818 (2H, ABq, J=14.1 Hz), 7.42 (2H,s), 8.12 (1H, dd, J=5.6, 8.8
Hz), 9.08 (1H, d, J=8.8 Hz), 9.15 (1H, s), 9.46 (1H, d, J=5.6 Hz),
9.56 (1H, d, J=8.6 Hz).
[0617] IR (KBr) cm.sup.-1: 3415, 1779, 1675, 1617, 1538, 1483,
1442, 1392, 1372, 1348, 1291, 1236, 1188, 1155, 1100, 1063,
1034.
[0618] MS(ESI): 621.sup.+(M+H).sup.+.
[0619] Elementary Analysis as
C.sub.23H.sub.21ClN.sub.8O.sub.7S.sub.2.mult- idot.3.1H.sub.2O.
[0620] Calculated: C, 40.81; H, 4.05; N, 16.55; Cl, 5.24; S, 9.47
(%). Found: C, 40.85; H, 3.85; N, 16.73; Cl, 5.01; S, 9.46 (%).
EXAMPLE 32
[0621] 81
[0622] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39 (3H, d, J=7.1 Hz),
3.01 and 3.46 (2H, ABq, J=17.6 Hz), 4.56 (1H, q, J=7.1 Hz), 5.00
and 5.55 (2H, ABq, J=13.4 Hz), 5.06 (1H, d, J=5.1 Hz), 5.70 (1H,
dd, J=5.1 Hz), 6.74 (2H, brs), 7.42 (2H,brs), 7.55 (1H, d, J=8.5
Hz), 7.68 (1H, dd, J=8.5, 5.7 Hz), 8.38 (1H, d, J=5.7 Hz), 8.51
(1H, brs), 9.67 (1H, brs).
[0623] IR (KBr) cm.sup.-1: 3351, 3208, 1777, 1629, 1538, 1512,
1445, 1391, 1346, 1232, 1190, 1155, 1098, 1065, 1034.
[0624] MS(ESI): 582.sup.+(M+H).sup.+.
[0625] Elementary Analysis as
C.sub.21H.sub.20ClN.sub.7O.sub.7S.sub.2.mult- idot.3.6H.sub.2O.
[0626] Calculated: C, 38.99; H, 4.24; N, 15.16; Cl, 5.48; S, 9.91
(%). Found: C, 38.84; H, 3.84; N, 15.23; Cl, 5.34; S, 9.67 (%).
EXAMPLE 33
[0627] 82
[0628] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=6.9 Hz),
3.10 and 3.34 (2H, ABq, J=17.3 Hz), 4.39 (3H, s), 4.55 (1H, q,
J=6.9 Hz), 5.01 (1H, d, J=4.9 Hz), 5.60 and 5.73 (2H, ABq, J=14.3
Hz), 5.68 (1H, dd, J=4.9, 9.0 Hz), 7.42 (2H, s), 7.97 (1H,dd,
J=5.5, 8.6 Hz), 9.04 (1H, d, J=8.6 Hz), 9.42 (1H, d, J=5.5 Hz),
9.59 (2H, brs).
[0629] IR (KBr) cm.sup.-1: 3419, 1778, 1634, 1615, 1538, 1454,
1408, 1356, 1329, 1295, 1235, 1176, 1156, 1100, 1073, 1035,
1011.
[0630] MS(ESI): 621.sup.+(M+H).sup.+.
[0631] Elementary Analysis as
C.sub.23H.sub.21ClN.sub.8O.sub.7S.sub.2.mult- idot.3.2H.sub.2O.
[0632] Calculated: C, 40.70; H, 4.07; N, 16.51; Cl, 5.22; S, 9.45
(%). Found: C, 40.48; H, 3.61; N, 16.42; Cl, 5.16; S, 9.46 (%).
EXAMPLE 34
[0633] 83
[0634] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39 (3H, d, J=7.1 Hz),
2.95 and 3.41 (2H, ABq, J=17.7 Hz), 4.57 (1H, q, J=7.1 Hz), 4.70
and 5.22 (2H, ABq, J=13.8 Hz), 5.05 (1H, d, J=4.89 Hz), 5.66 (2H,
brs), 5.71 (1H, dd, J=4.8, 8.7 Hz), 6.73 (1H, d, J=6.9 Hz), 7.42
(4H, brs), 7.98 (2H, m).
[0635] IR (KBr) cm.sup.-1: 3379, 3213, 1775, 1645, 1577, 1542,
1446, 1360, 1308, 1235, 1184, 1156, 1065, 1035.
[0636] MS(ESI): 597.sup.+(M+H).sup.+.
[0637] Elementary Analysis as
C.sub.21H.sub.21ClN.sub.8O.sub.7S.sub.2 3.1H.sub.2O.
[0638] Calculated: C, 38.63; H, 4.20; N, 17.16; Cl, 5.43; S, 9.82
(%). Found: C, 38.51; H, 3.83; N, 17.22; Cl, 5.41; S, 9.75 (%).
EXAMPLE 35
[0639] 84
[0640] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.40 (3H, d, J=7.1 Hz),
3.09 and 3.48 (2H, ABq, J=17.7 Hz), 4.57 (1H, q, J=7.1 Hz), 4.85
and 5.22 (2H, ABq, J=13.8 Hz), 5.09 (1H, d, J=4.9 Hz), 5.76 (1H,
dd, J=4.9 Hz), 6.58 (2H, brs), 6.95 (1H, d, J=6.5 Hz), 7.40 (2H,
s), 7.96 (2H,brs), 8.28 (1H, d, J=6.5 Hz), 8.82 (1H, brs), 9.25
(1H, brs), 9.77 (1H, brs).
[0641] IR (KBr) cm.sup.-1: 3364, 3205, 1775, 1657, 1540, 1493,
1447, 1355, 1270, 1182, 1146, 1109, 1066, 1034.
[0642] MS(ESI): 640.sup.+(M+H).sup.+.
[0643] Elementary Analysis as
C.sub.22H.sub.22ClN.sub.9O.sub.8S.sub.2.mult- idot.3.0H.sub.2O.
[0644] Calculated: C, 38.07; H, 4.07; N, 18.16; Cl, 5.11; S, 9.24
(%). Found: C, 37.72; H, 3.67; N, 17.97; Cl, 5.03; S, 9.02 (%).
EXAMPLE 36
[0645] 85
[0646] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.36 (3H, d, J=7.0 Hz),
3.10 and 3.54 (2H, ABq, J=17.6 Hz), 4.55 (1H, q, J=7.0 Hz), 5.14
(1H, d, J=5.0 Hz), 5.20 and 5.68 (2H, ABq, J=13.8 Hz), 5.77 (1H,
dd, J=5.0, 9.1 Hz), 7.40 (2H, brs), 8.18 (1H, d, J=6.6 Hz), 8.83
(1H, brs), 8.87 (1H, d, J=6.6 Hz), 9.68 (1H, d, J=9.1 Hz), 9.80
(1H, brs).
[0647] IR (KBr) cm.sup.-1: 3412, 1777, 1614, 1539, 1444, 1377,
1305, 1187, 1108, 1066, 1036.
[0648] MS(ESI): 607.sup.+(M+H).sup.+.
[0649] Elementary Analysis as
C.sub.22H.sub.19ClN.sub.8O.sub.7S.sub.2.mult- idot.2.7H.sub.2O.
[0650] Calculated: C, 40.30; H, 3.75; N, 17.09; Cl, 5.41; S, 9.78
(%). Found: C, 40.22; H, 3.55; N, 17.05; Cl, 5.35; S, 9.57 (%).
EXAMPLE 37
[0651] 86
[0652] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.38 (3H, d, J=7.1 Hz),
3.07 and 3.49 (2H, ABq, J=17.4 Hz), 4.57 (1H, q, J=7.1 Hz), 5.09
(1H, d, J=4.8 Hz), 5.12 and 5.55 (2H, ABq, J=13.5 Hz), 5.75 (1H,
dd, J=4.8, 8.2 Hz), 7.41 (2H, s), 7.48 (1H, d, J=6.2 Hz), 8.70 (1H,
d, J=6.2 Hz), 8.90 (1H, brs), 9.62 (1H, d, J=8.2 Hz).
[0653] IR (KBr) cm.sup.-1: 3421, 3195, 3088, 2988, 1776, 1720,
1639, 1532, 1375, 1237, 1175, 1137, 1066, 1035.
[0654] MS(ESI): 651.sup.+(M+H).sup.+.
[0655] Elementary Analysis as
C.sub.23H.sub.19ClN.sub.8O.sub.9S.sub.2.mult- idot.3.1H.sub.2O.
[0656] Calculated: C, 39.08; H, 3.59; N, 15.85; Cl, 5.02; S, 9.07
(%). Found: C, 39.05; H, 3.44; N, 15.81; Cl, 4.84; S, 8.83 (%).
EXAMPLE 38
[0657] 87
[0658] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=6.9 Hz),
3.06 and 3.49 (2H, ABq, J=17.6 Hz), 4.51 (1H, q, J=6.9 Hz), 5.06
(1H, d, J=4.7 Hz), 5.04 and 5.61 (2H, ABq, J=12.9 Hz), 5.71 (1H,
dd, J=4.7, 8.9 Hz), 7.42 (2H, s), 8.40 (1H, d, J=6.2 Hz), 8.64 (2H,
s), 8.91 (1H, d, J=6.2 Hz), 9.39 (1H, s), 9.60 (1H, brs).
[0659] IR (KBr) cm.sup.-1: 3399, 3191, 1775, 1638, 1537, 1478,
1391, 1317, 1273, 1236, 1187, 1089, 1035.
[0660] MS(ESI): 639.sup.+(M+H).sup.+.
[0661] Elementary Analysis as
C.sub.22H.sub.19ClN.sub.8O.sub.7S.sub.3.mult- idot.3.4H.sub.2O
[0662] Calculated: C, 37.73; H, 3.71; N, 16.00; Cl, 5.06; S, 13.74
(%). Found: C, 37.61; H, 3.35; N, 16.12; Cl, 4.92; S, 13.56
(%).
EXAMPLE 39
[0663] 88
[0664] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=6.9 Hz),
3.06 and 3.50 (2H, ABq, J=17.7 Hz), 4.53 (1H, q, J=6.9 Hz), 5.06
(1H, d, J=4.7 Hz), 4.91 and 5.45 (2H, ABq, J=12.5 Hz), 5.70 (1H,
dd, J=4.7, 8.79 Hz), 6.85 (1H,s), 7.01 (1H, s), 7.41 (2H, s), 7.96
(1H, s), 8.15 (2H, d, J=5.7 Hz), 9.08 (2H, d, J=5.7 Hz), 9.73 (1H,
brs), 11.85 (1H, brs).
[0665] IR (KBr) cm.sup.-1: 3410, 1774, 1636, 1560, 1474, 1354,
1218, 1152, 1107, 1037.
[0666] MS(ESI): 632.sup.+(M+H).sup.+.
[0667] Elementary Analysis as
C.sub.25H.sub.22ClN.sub.7O.sub.7S.sub.2.mult- idot.8.4H.sub.2O.
[0668] Calculated: C, 38.33; H, 3.99; N, 12.52; Cl, 4.53; S, 8.19
(%). Found: C, 37.89; H, 3.62; N, 12.41; Cl, 4.41; S, 7.93 (%).
EXAMPLE 40
[0669] 89
[0670] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=7.1 Hz),
2.96 and 3.26 (2H, ABq, J=17.6 Hz), 4.02 (3H, s), 4.50 (2H, brs),
4.98 (1H, d, J=4.8 Hz), 5.67 (1H, brs), 7.34 (1H,d, J=3.0 Hz), 7.41
(2H, brs), 7.78 (1H d, J=6.0 Hz), 8.29 (1H, d, J=3.0 Hz), 8.75 (1H,
d, J=7.9 Hz), 9.13 (1H, d, J=6.0, 7.9 Hz), 9.75 (1H, brs).
[0671] IR (KBr) cm.sup.-1: 3412, 1775, 1673, 1613, 1538, 1501,
1470, 1392, 1368, 1324, 1281, 1221, 1152, 1063, 1035.
[0672] MS(ESI): 620.sup.+(M+H).sup.+.
[0673] Elementary Analysis as
C.sub.23H.sub.20ClN.sub.7O.sub.7S.sub.2.mult- idot.2.1H.sub.2O.
[0674] Calculated: C, 42.90; H, 3.79; N, 15.23; Cl, 5.51; S, 9.96
(%). Found: C, 42.91; H, 3.76; N, 15.34; Cl, 5.47; S, 9.90 (%).
EXAMPLE 41
[0675] 90
[0676] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=7.1 Hz),
3.03 and 3.28 (2H, ABq, J=17.4 Hz), 4.56 (1H, q, J=7.1 Hz), 5.01
(1H, d, J=4.8 Hz), 5.69 (3H, m), 7.32 (1H,d, J=2.9 Hz), 7.41 (2H,
s), 7.67 (1H t-like), 8.27 (1H, d, J=2.9 Hz), 8.60 (1H, d, J=8.4
Hz), 9.06 (1H, d, J=5.7 Hz), 9.68 (1H, brs), 13.45 (1H, brs).
[0677] IR (KBr) cm.sup.-1: 3410, 2938, 1777, 1673, 1613, 1537,
1457, 1385, 1361, 1225, 1185, 1156, 1114, 1033.
[0678] MS(ESI): 606.sup.+(M+H).sup.+.
[0679] Elementary Analysis as
C.sub.23H.sub.20ClN.sub.7O.sub.7S.sub.2.mult- idot.2.5H.sub.2O.
[0680] Calculated: C, 42.43; H, 3.87; N, 15.06; Cl, 5.45; S, 9.85
(%). Found: C, 42.44; H, 3.69; N, 14.90; Cl, 5.24; S, 9.94 (%).
EXAMPLE 42
[0681] 91
[0682] .sup.1H-NMR (.sub.D2O) .delta.: 1.55 (3H, d, J=7.1 Hz), 2.19
(6H, tike), 3.39-3.56 (7H, m), 3.89 (1H, d, J=16.8 Hz), 3.93 (1H,
d, J=13.9 Hz), 4.62 (1H, d, J=13.9 Hz), 4.86 (1H, m), 5.36 (1H,d,
J=5.0 Hz), 5.90 (1H, d, J=5.6 Hz).
[0683] IR (KBr) cm.sup.-1: 3371, 1779, 1671, 1614, 1538, 1466,
1389, 1343, 1236, 1183, 1099, 1070, 1035.
[0684] MS(ESI): 642.sup.+(M+H).sup.+.
[0685] Elementary Analysis as
C.sub.24H.sub.28ClN.sub.7O.sub.8S.sub.2.mult- idot.5.6H.sub.2O.
[0686] Calculated: C, 38.80; H, 5.32; N, 13.20; Cl, 4.77; S, 8.63
(%). Found: C, 38.57; H, 4.76; N, 13.24; Cl, 4.56; S, 8.32 (%).
EXAMPLE 43
[0687] 92
[0688] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.31 (3H, d, J=7.1 Hz),
1.44 (3H, t, J=7.2 Hz), 2.96 and 3.25 (2H, ABq, J=17.1 Hz), 4.32
(1H, q, J=7.1 Hz), 4.45 (2H, q, J=7.2 Hz), 4.93 (1H, d, J=5.1 Hz),
5.68 (2H, t-like), 5.75 (1H, dd, J=5.1, 9.0 Hz), 7.31 (2H,s), 7.39
(1H, d, J=3.5 Hz), 7.78 (1H, dd, J=6.1, 8.1 Hz), 8.37 (1H, d, J=3.5
Hz), 8.81 (1H, d, J=8.1 Hz), 9.21 (1H, d, J=6.1 Hz), 12.10 (1H, d,
J=9.0 Hz).
[0689] IR (KBr) cm.sup.-1: 3409, 2982, 1772, 1604, 1539, 1496,
1460, 1394, 1362, 1317, 1289, 1230, 1185, 1153, 1106, 1033.
[0690] MS(ESI): 634.sup.+(M+H).sup.+. Elementary Analysis as
C.sub.25H.sub.23ClN.sub.7N.sub.aO.sub.7S.sub.2.multidot.3.7H.sub.2O.
[0691] Calculated: C, 41.55; H, 4.24; N, 13.57; Cl, 4.91; S, 8.87;
Na, 3.18 (%). Found: C, 41.48; H, 3.96; N, 13.60; Cl, 4.84; S,
8.87; Na, 3.26 (%).
EXAMPLE 44
[0692] 93
[0693] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.35 (3H, d, J=6.9 Hz),
3.12 and 3.49 (2H, ABq, J=17.9 Hz), 4.54 (1H, q, J=6.9 Hz), 5.12
(1H, d, J=4.8 Hz), 5.57 and 5.68 (2H, ABq, J=14.1 Hz), 5.81 (1H,
dd, J=4.8, 8.9 Hz), 7.42 (2H,s), 7.52 (1H, t-like), 8.55 (2H, brs),
8.71 (1H, d; J=6.6 Hz), 9.54 (1H, d, J=8.9 Hz).
[0694] IR (KBr) cm.sup.-1: 3416, 1777, 1674, 1608, 1538, 1449,
1387, 1311, 1230, 1187, 1158, 1102, 1072, 1032.
[0695] MS(ESI): 607.sup.+(M+H).sup.+.
[0696] Elementary Analysis as
C.sub.22H.sub.19ClN.sub.8O.sub.7S.sub.2.mult- idot.2.3H.sub.2O.
[0697] Calculated: C, 40.75; H, 3.67; N, 17.28; Cl, 5.47; S, 9.89
(%). Found: C, 40.72; H, 3.55; N, 17.35; Cl, 5.51; S, 9.90 (%).
EXAMPLE 45
[0698] 94
[0699] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.34 (3H, d, J=6.9 Hz),
3.00 and 3.51 (2H, ABq, J=17.6 Hz), 4.07 (3H, s), 4.53 (1H, q,
J=6.9 Hz), 5.02 (1H, d, J=5.4 Hz), 5.68-5.74 (3H, m), 7.41 (2H,s),
7.97 (1H, t-like), 8.89 (1H, d, J=7.8 Hz), 9.04 (1H, s), 9.66 (2H,
m).
[0700] IR (KBr) cm.sup.-1: 3416, 1778, 1674, 1615, 1538, 1497,
1464, 1362, 1316, 1266, 1235, 1188, 1155, 1100, 1063, 1033.
[0701] MS(ESI): 621.sup.+(M+H).sup.+.
[0702] Elementary Analysis as
C.sub.23H.sub.21ClN.sub.8O.sub.7S.sub.2.mult- idot.2.3H.sub.2O.
[0703] Calculated: C, 41.70; H, 3.89; N, 16.91; Cl, 5.35; S, 9.68
(%). Found: C, 41.67; H, 3.85; N, 16.90; Cl, 5.27; S, 9.60 (%).
EXAMPLE 46
[0704] 95
[0705] .sup.1H-NMR (D.sub.2O) .delta.: 1.43 (3H, d, J=7.2 Hz), 2.35
(2H, m), 3.12 (2H, t-like), 3.19 and 3.68 (2H, ABq, J=17.7 Hz),
4.61 (3H, q-like), 5.28 (1H, d, J=5.1 Hz), 5.33 and 5.67 (2H, ABq,
J=14.7 Hz), 5.86 (1H, d, J=5.1 Hz), 8.21 (1H, d, J=6.3 Hz), 8.70
(1H, d, J=6.3 Hz), 8.90 (1H, brs), 9.71 (1H, s).
[0706] IR (KBr) cm.sup.-1: 3410, 1773, 1606, 1538, 1478, 1450,
1384, 1315, 1284, 1214, 1170, 1117, 1083, 1033.
[0707] MS(ESI): 664.sup.+(M+H).sup.+.
[0708] Elementary Analysis as
C.sub.25H.sub.26ClN.sub.9O.sub.7S.sub.2.mult- idot.3.6H.sub.2O.
[0709] Calculated: C, 41.19; H, 4.59; N, 17.29; Cl, 4.86; S,
8.80(%). Found: C, 41.25; H, 4.49; N, 17.07; Cl, 4.87; S, 8.50
(%).
EXAMPLE 47
[0710] 96
[0711] .sup.1H-NMR (D.sub.2O) .delta.: 1.42 (3H, d, J=6.9 Hz), 2.34
(2H, m), 3.10 (2H, t-like), 3.18 and 3.63 (2H, ABq, J=17.9 Hz),
4.55-4.67 (3H, m), 5.27(1H, d, J=5.0 Hz), 5.35 and 5.66 (2H, ABq,
J=14.3 Hz), 5.87 (1H, d, J=5.0 Hz), 8.22 (1H, d, J=6.9 Hz), 8.79
(2H, d,-like), 9.49 (1H, s).
[0712] IR (KBr) cm.sup.-1: 3410, 1773, 1606, 1539, 1515, 1458,
1395, 1363, 1310, 1216, 1185, 1137, 1107, 1066, 1033.
[0713] MS(ESI): 664.sup.+(M+H).sup.+.
[0714] Elementary Analysis as
C.sub.25H.sub.26ClN.sub.9O.sub.7S.sub.2.mult- idot.3.2H.sub.2O.
[0715] Calculated C, 41.60; H, 4.52; N, 17.47; Cl, 4.91; S, 8.89
(%). Found: C, 41.63; H, 4.48; N, 17.40; Cl, 4.82; S, 8.73 (%).
EXAMPLE 48
[0716] 97
[0717] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.34 (3H, d, J=6.9 Hz),
2.84 and 3.51 (2H, ABq, J=17.4 Hz), 4.51 (1H, q, J=6.9 Hz), 5.11
(1H, d, J=4.6 Hz), 5.14 and 5.54 (2H, ABq, J=14.4 Hz), 5.72 (1H,
dd, J=4.6, 9.0 Hz), 6.59 (1H, brs), 7.34-7.40 (3H, m), 8.77 (2H,
d,-like), 9.58 (1H, brs).
[0718] IR (KBr) cm.sup.-1: 3414, 1774, 1638, 1574, 1538, 1446,
1391, 1367, 1334, 1227, 1182, 1078, 1036.
[0719] MS(ESI): 662.sup.+(M+H).sup.+.
[0720] Elementary Analysis as
C.sub.22H.sub.20ClN.sub.9O.sub.7S.sub.2.mult- idot.2.4H.sub.2O.
[0721] Calculated: C, 39.72; H, 3.76; N, 18.95; Cl, 5.33; S, 9.649
(%). Found: C, 39.77; H, 3.69; N, 19.04; Cl, 5.27; S, 9.49 (%).
EXAMPLE 49
[0722] 98
[0723] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=7.0 Hz),
3.09 and 3.51 (2H, ABq, J=17.6 Hz), 4.54 (1H, q, J=7.0 Hz), 4.99
and 5.51 (2H, ABq, J=12.8 Hz), 5.70 (1H, dd, J=4.7, 8.7 Hz), 7.42
(2H, s), 8.30 (2H, d, J=6.5 Hz), 8.59 (2H, brs), 9.58 (1H, d, J=8.7
Hz), 13.7 (1H, brs).
[0724] IR (KBr) cm.sup.-1: 3314, 3194, 1777, 1671, 1637, 1570,
1538, 1470, 1391, 1344, 1285, 1221, 1156, 1100, 1065, 1034.
[0725] MS(ESI): 633.sup.+(M+H).sup.+.
[0726] Elementary Analysis as
C.sub.24H.sub.21ClN.sub.8O.sub.7S.sub.2.mult- idot.2.5H.sub.2O.
[0727] Calculated: C, 42.51; H, 3.86; N, 16.52; Cl, 5.23; S, 9.46
(%). Found: C, 42.44; H, 3.67; N, 16.68; Cl, 5.36; S, 9.36 (%).
EXAMPLE 50
[0728] 99
[0729] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=7.1 Hz),
3.09 and 3.51 (2H, ABq, J=17.4 Hz), 4.76 (1H, q, J=7.1 Hz), 4.94
and 5.49 (2H, ABq, J=12.5 Hz), 5.07 (1H, d, J=4.7 Hz), 5.72 (1H,
dd, J=4.7, 8.6 Hz), 7.27 (1H, brs), 7.41 (2H, s), 7.62 (1H, brs),
7.94 (1H, brs), 8.06 (1H, brs), 8.18 (2H, d, J=5.9 Hz), 9.16 (2H,
d, J=5.9 Hz), 9.81 (1H, brs), 12.5 (1H, brs).
[0730] IR (KBr) cm.sup.-1: 3402, 1775, 1718, 1636, 1608, 1570,
1550, 1441, 1393, 1343, 1288, 1220, 1150, 1035.
[0731] MS(ESI): 675.sup.+(M+H).sup.+.
[0732] Elementary Analysis as
C.sub.26H.sub.23ClN.sub.8O.sub.8S.sub.2 5.1H.sub.2O.
[0733] Calculated: C, 40.72; H, 4.36; N, 14.61; Cl, 4.62; S, 8.36
(%). Found: C40 56; H, 3.97; N, 14.44; Cl, 5.09; S, 8.05(%).
EXAMPLE 51
[0734] 100
[0735] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.34 (3H, d, J=7.0 Hz),
3.05 and 3.61 (2H, ABq, J=17.9 Hz), 4.52 (1H, q, J=7.0 Hz), 4.82
and 5.37 (2H, ABq, J=14.4 Hz), 5.14 (1H, d, J=5.0 Hz), 5.76 (1H,
dd, J=5.0, 8.9 Hz), 7.37 (2H, brs), 7.43 (1H, d, J=6.9 Hz), 8.40
(2H, brs), 8.42 (1H, d, J=6.9 Hz), 9.63 (2H, brs).
[0736] IR (KBr) cm.sup.-1: 3336, 3192, 1774, 1662, 1617, 1573,
1539, 1489, 1393, 1332, 1246, 1188, 1153, 1119, 1066, 1034.
[0737] MS(ESI): 622.sup.+(M+H).sup.+.
[0738] Elementary Analysis as
C.sub.22H.sub.20ClN.sub.9O.sub.7S.sub.2.mult- idot.1.9H.sub.2O.
[0739] Calculated: C, 40.26; H, 3.66; N, 19.21; Cl, 5.40; S, 9.77
(%). Found: C, 40.48; H, 3.69; N, 19.26; Cl, 5.10; S, 9.48 (%).
EXAMPLE 52
[0740] 101
[0741] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=7.0 Hz),
3.18 and 3.52 (2H, ABq, J=18.0 Hz), 4.56 (1H, q, J=7.0 Hz), 5.11
(2H, m), 5.48(1H, q, J=13.8 Hz), 5.81 (1H, q, J=4.7, 8.8 Hz),
7.12(1H, rs), 7.41 (2H, s), 7.53 (1H, s), 7.83 (1H, d, J=6.0 Hz),
8.38 (1H, d, J=6.0 Hz), 9.24 (1H, brs), 9.63 (1H, d, J=8.8 Hz).
[0742] IR (KBr) cm.sup.-1: 3420, 1778, 1672, 1623, 1535, 1480,
1445, 1395, 1308, 1184, 1154, 1131, 1065, 1035.
[0743] MS(ESI): 649.sup.+(M+H).sup.+.
[0744] Elementary Analysis as
C.sub.25H.sub.21ClN.sub.6O.sub.9S.sub.2.mult- idot.2.1H.sub.2O.
[0745] Calculated: C, 43.71; H, 3.70; N, 12.23; Cl, 5.16; S, 9.34
(%). Found: C, 44.06; H, 3.69; N, 12.31; Cl, 5.00; S, 9.94 (%).
EXAMPLE 53
[0746] 102
[0747] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.35 (3H, d, J=7.0 Hz),
3.04 and 3.50 (2H, ABq, J=17.7 Hz), 4.54 (1H, q, J=7.0 Hz), 5.08
(1H, d, J=5.1 Hz), 5.15 and 5.65 (2H, ABq, J=13.7 Hz), 5.73 (1H,
dd, J=5.1, 8.6 Hz), 7.01 (1H, d, J=3.3 Hz), 7.42 (2H, s), 7.94 (1H,
d, J=3.3 Hz), 8.03 (1H, d, J=6.6 Hz), 8.88 (1H, d, J=6.6 Hz), 9.71
(1H, brs), 13.4 (1H, brs).
[0748] IR (KBr) cm.sup.-1: 3395, 3009, 2937, 1777, 1673, 1632,
1537, 1484, 1445, 1378, 1359, 1227, 1187, 1153, 1117, 1065,
1034.
[0749] MS(ESI): 606.sup.+(M+H).sup.+.
[0750] Elementary Analysis as
C.sub.23H.sub.20ClN.sub.7O.sub.7S.sub.2.mult- idot.2.2H.sub.2O.
[0751] Calculated: C, 42.78; H, 3.81; N, 15.19; Cl, 5.49; S, 9.93
(%). Found: C, 42.87; H, 3.81; N, 15.20; Cl, 5.30; S, 9.86 (%).
EXAMPLE 54
[0752] 103
[0753] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.41 (3H, d, J=7.0 Hz),
2.97 and 3.21 (2H, ABq, J=17.6 Hz), 3.58 (2H, brs), 4.58 (1H, q,
J=7.0 Hz), 5.06 (1H, d, J=4.9 Hz), 5.10 and 5.23 (2H, ABq, J=15.9
Hz), 5.70 (1H, dd, J=4.9, 8.6 Hz), 5.83 (1H, d, J=3.0 Hz), 7.26
(2H, s), 7.43 (2H, s), 8.08 (1H, d, J=3.0 Hz), 9.75 (1H, brs).
[0754] IR (KBr) cm.sup.-1: 3411, 2939, 1775, 1635, 1537, 1456,
1325, 1221, 1151, 1097, 1036.
[0755] MS(ESI): 615.sup.+(M+H).sup.+.
[0756] Elementary Analysis as
C.sub.21H.sub.23ClN.sub.8O.sub.8S.sub.2.mult- idot.2.6H.sub.2O.
[0757] Calculated: C, 38.11; H, 4.29; N, 16.93; Cl, 5.36; S, 9.69
(%). Found: C, 38.04; H, 3.93; N, 16.67; Cl, 5.49; S, 9.68 (%).
EXAMPLE 55
[0758] 104
[0759] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.30 (3H, d, J=7.0 Hz),
2.76 and 3.57 (2H, ABq, J=18.0 Hz), 4.48 (1H, q, J=7.0 Hz), 5.13
(1H, d, J=4.9 Hz), 5.24 and 5.90 (2H, ABq, J=14.3 Hz), 5.72 (1H,
dd, J=4.9, 8.4 Hz), 6.89 (1H, d, J=3.3 Hz), 7.40 (2H, s), 7.58 (1H,
dd, J=6.0, 7.8 Hz), 7.92 (1H, d, J=3.3 Hz), 8.71 (2H, m), 9.54 (1H,
d, J=8.4 Hz).
[0760] IR (KBr) cm.sup.-1: 3413, 2934, 2718, 1777, 1675, 1616,
1537, 1480, 1461, 1362, 1230, 1189, 1112, 1034.
[0761] MS(ESI): 606.sup.+(M+H).sup.+.
[0762] Elementary Analysis as
C.sub.23H.sub.20ClN.sub.7O.sub.7S.sub.2.mult- idot.2.3H.sub.2O.
[0763] Calculated: C, 42.67; H, 3.83; N, 15.14; Cl, 5.48; S, 9.90
(%). Found: C, 42.65; H, 3.82; N, 15.18; Cl, 5.40; S, 9.74 (%).
EXAMPLE 56
[0764] 105
[0765] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39 (3H, d, J=7.1 Hz),
3.15 and 3.52 (2H, ABq, J=17.7 Hz), 4.56 (1H, q, J=7.1 Hz), 5.10
(1H, d, J=4.9 Hz), 5.36 (2H, brs), 5.80 (1H, dd, J=4.9, 8.6 Hz),
7.11 (1H, t, J=7.2 Hz), 7.69 (1H, d, J=7.2 Hz), 8.42 (3H, m), 9.84
(1H, brs).
[0766] IR (KBr) cm.sup.-1: 3352, 3151, 2712, 1772, 1665, 1607,
1583, 1543, 1490, 1443, 1408, 1390, 1368, 1341, 1300, 1211, 1160,
1106, 1083, 1060, 1031.
[0767] MS(ESI): 622.sup.+(M+H).sup.+.
[0768] Elementary Analysis as
C.sub.22H.sub.20ClN.sub.9O.sub.7S.sub.2.mult- idot.3.0H.sub.2O.
[0769] Calculated: C, 39.08; H, 3.88; N, 18.65; Cl, 5.24; S, 9.49
(%). Found: C, 39.26; H, 3.83; N, 18.75; Cl, 5.33; S, 9.19 (%).
EXAMPLE 57
[0770] 106
[0771] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.34 (3H, d, J=6.9 Hz),
2.97 and 3.48 (2H, ABq, J=17.6 Hz), 3.98 (3H,s), 4.52 (1H, q, J=6.9
Hz), 5.05-5.12 (2H, m), 5.63-5.72 (2H, m), 7.09 (1H, d, J=3.1 Hz),
7.42 (2H, s), 7.94 (1H, d, J=3.1 Hz), 8.17 (1H, d, J=7.1 Hz), 9.49
(1H, d, J=7.1 Hz), 9.64 (1H, brs), 9.7 (1H, brs).
[0772] IR (KBr) cm.sup.-1: 3406, 3073, 2945, 1778, 1675, 1631,
1538, 1447, 1361, 1324, 1254, 1227, 1184, 1132, 1106, 1065,
1033.
[0773] MS(FAB): 620 (M+H).sup.+.
[0774] Elementary Analysis as
C.sub.24H.sub.22ClN.sub.7O.sub.7S.sub.2.mult- idot.2.4H.sub.2O.
[0775] Calculated: C, 43.46; H, 4.07; N, 14.78; Cl, 5.34; S, 9.67
(%). Found: C, 43.45; H, 4.03; N, 14.88; Cl, 5.25; S, 9.55(%).
EXAMPLE 58
[0776] 107
[0777] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.35 (3H, d, J=6.9 Hz),
3.04 and 3.56 (2H, ABq, J=17.6 Hz), 4.53 (1H, q, J=7.0 Hz),
5.09-5.15 (2H, m), 5.68-5.76 (2H, m), 6.92 (1H, d, J=2.7 Hz), 7.40
(2H, s), 8.11 (1H, d, J=6.9 Hz), 8.30 (1H, d, J=2.7 Hz), 8.55 (1H,
d, J=6.9 Hz), 9.84 (2H, brs), 14.7 (1H, brs).
[0778] IR (KBr) cm.sup.-1: 3326, 3195, 2938, 1777, 1674, 1612,
1537, 1461, 1375, 1312, 1234, 1187, 1145, 1065, 1034.
[0779] MS(ESI): 606 (M+H).sup.+.
[0780] Elementary Analysis as
C.sub.23H.sub.20ClN.sub.7O.sub.7S.sub.2.mult- idot.2.5H.sub.2O.
[0781] Calculated: C, 42.43; H, 3.87; N, 15.06 Cl, 5.45; S, 9.85
(%). Found: C, 42.46; H, 3.74; N, 15.01; Cl, 5.33; S, 9.93 (%).
EXAMPLE 59
[0782] 108
[0783] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.34 (3H, d, J=7.0 Hz),
3.08 and 3.49 (2H, ABq, J=17.6 Hz), 4.04 (3H, s), 4.52 (1H, q,
J=7.0 Hz), 5.05-5.12 (2H, m), 5.66-5.72 (2H, m), 6.92 (1H, d, J=2.9
Hz), 7.42 (2H, brs), 8.14 (1H, d, J=6.8 Hz), 8.28 (1H, d, J=2.9
Hz), 8.97 (1H, d, J=6.8 Hz), 9.64 (1H, brs), 9,80 (1H, brs).
[0784] IR (KBr) cm.sup.-1: 3410, 1777, 1676, 1614, 1537, 1486,
1447, 1423, 1378, 1326, 1260, 1230, 1161, 1096, 1065, 1033.
[0785] MS(ESI): 620 (M+H).sup.+.
[0786] Elementary Analysis as
C.sub.24H.sub.22ClN.sub.7O.sub.7S.sub.2.mult- idot.2.4H.sub.2O.
[0787] Calculated: C, 43.46; H, 4.07; N, 14.78; Cl, 5.34; S, 9.67
(%). Found: C, 43.47; H, 3.97; N, 14.79; Cl, 5.21; S, 9.59 (%).
EXAMPLE 60
[0788] 109
[0789] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39 (3H, d, J=7.1 Hz),
3.15 and 3.34 (2H, ABq, J=17.6 Hz), 4.56 (1H, q, J=7.1 Hz), 5.05
(1H, d, J=4.8 Hz), 5.47 (1H, d, J=14.1 Hz), 5.72-5.78 (2H,m), 7.41
(2H, brs), 7.84 (1H, dd, J=5.9, 8.1 Hz), 8.21 (1H, d, J=8.1 Hz),
8.83 (1H, d, J=5.9 Hz), 8.89 (2H, brs), 9.87 (1H, brs).
[0790] IR (KBr) cm.sup.-1: 3312, 3189, 1778, 1630, 1537, 1426,
1386, 1341, 1308, 1214, 1186, 1129, 1064, 1034.
[0791] MS(FAB): 639.sup.+(M+H).sup.+.
[0792] Elementary Analysis as
C.sub.22H.sub.19ClN.sub.8O.sub.7S.sub.3.mult- idot.3.2H.sub.2O.
[0793] Calculated: C, 37.92; H, 3.67; N, 16.08; Cl, 5.09; S,
13.81(%). Found: C, 37.95; H, 3.60; N, 16.04; Cl, 5.07; S, 13.60
(%).
EXAMPLE 61
[0794] 110
[0795] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.35 (3H, d, J=7.0 Hz),
2.90 and 3.46 (2H, ABq, J=17.6 Hz), 3.66 (3H, s), 4.53 (1H, q,
J=7.0 Hz), 4.96 and 5.56 (2H, ABq, J=13.7 Hz), 5.06 (1H, d, J=4.9
Hz), 5.69 (1H, dd, J=4.9, 8.9 Hz), 7.42 (2H, brs), 7.73 (2H, brs),
7.81 (1H, d, J=6.6 Hz), 8.81 (1H, d, J=6.6 Hz), 9.63 (1H, brs).
[0796] IR (KBr) cm.sup.-1: 3346, 3180, 1775, 1664, 1613, 1567,
1538, 1508, 1448, 1389, 1352, 1311, 1271, 1179, 1100, 1065,
1034.
[0797] MS(FAB): 636.sup.+(M+H).sup.+.
[0798] Elementary Analysis as
C.sub.23H.sub.22ClN.sub.9O.sub.7S.sub.2.mult- idot.2.7H.sub.2O.
[0799] Calculated: C, 40.35; H, 4.03; N, 18.41; Cl, 5.18; S, 9.37
(%). Found: C, 40.32; H, 3.90; N, 18.39; Cl, 5.14; S, 9.35 (%).
EXAMPLE 62
[0800] 111
[0801] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.35 (3H, d, J=7.0 Hz),
3.03-3.09 (4H, m), 3.61 (1H, d, J=18.0 Hz), 4.52 (1H, q, J=7.0 Hz),
4.83 and 5.40 (2H, ABq, J=14.0 Hz), 5.14 (1H, d, J=5.0 Hz), 5.77
(1H, dd, J=5.0, 8.7 Hz), 7.36 (2H, brs), 7.48 (1H, d, J=6.8 Hz),
8.43 (1H, d, J=6.8 Hz), 9.33 (1H, brs), 9.59 (1H, brs), 9.70 (1H,
brs).
[0802] IR (KBr) cm.sup.-1: 3370, 1775, 1644, 1579, 1538, 1479,
1394, 1329, 1239, 1188, 1121, 1066, 1034.
[0803] MS(FAB): 636.sup.+(M+H).sup.+.
[0804] Elementary Analysis as
C.sub.23H.sub.22ClN.sub.9O.sub.7S.sub.2.mult- idot.2.2H.sub.2O.
[0805] Calculated: C, 40.88; H, 3.94; N, 18.66; Cl, 5.25; S, 9.49
(%). Found: C, 41.07; H, 4.21; N, 18.30; Cl, 4.86; S, 8.86 (%).
EXAMPLE 63
[0806] 112
[0807] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.41 (3H, d, J=7.0 Hz),
2.16 (3H, s), 3.10 (1H, d, J=17.1 Hz), 4.59 (1H, q, J=7.0 Hz), 5.08
(1H, d, J=5.1 Hz), 5.51 (2H, brs), 5.76 (1H,dd, J=5.1, 8.4 Hz),
6.87 (1H,s), 7.33 (1H, t-like), 7.39 (2H, brs), 8.01 (1H, brs),
8.59 (1H, d, J=6.0 Hz), 9.70 (1H, brs), 12.7 (1H, brs).
[0808] IR (KBr) cm.sup.-1: 3325, 1776, 1653, 1609, 1561, 1470,
1416, 1369, 1352, 1236, 1183, 1158, 1100, 1065, 1032.
[0809] MS(FAB): 663.sup.+(M+H).sup.+.
[0810] Elementary Analysis as
C.sub.25H.sub.23ClN.sub.8O.sub.8S.sub.2.mult- idot.3.2H.sub.2O.
[0811] Calculated: C, 41.66; H, 4.11; N, 15.55; Cl, 4.92; S, 8.90
(%). Found: C, 41.79; H, 4.14; N, 15.37; Cl, 4.82; S, 8.75 (%).
EXAMPLE 64
[0812] 113
[0813] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.36 (3H, d, J=7.1 Hz),
2.98 and 3.50 (2H, ABq, J=17.3 Hz), 3.21 (6H,s), 4.54 (1H, q, J=7.1
Hz), 5.00 and 5.48 (2H, ABq, J=13.5 Hz), 5.16 (1H, d, J=4.8 Hz),
5.72 (1H, dd, J=4.8, 9.0 Hz), 7.39 (2H, brs), 7.49 (1H, d, J=6.9
Hz), 8.44 (1H, d, J=6.9 Hz), 9.09 (1H, brs), 9.85 (1H, brs).
[0814] IR (KBr) cm.sup.-1: 3413, 2938, 1777, 1639, 1557, 1538,
1440, 1391, 1335, 1247, 1190, 1150, 1121, 1065, 1034.
[0815] MS(FAB): 650.sup.+(M+H).sup.+.
[0816] Elementary Analysis as
C.sub.24H.sub.24ClN.sub.9O.sub.7S.sub.2 3.2H.sub.2O.
[0817] Calculated: C, 40.73; H, 4.33; N, 17.81; Cl, 5.01; S, 9.06
(%). Found: C, 40.73; H, 4.24; N, 17.75; Cl, 5.08; S, 9.10 (%).
EXAMPLE 65
[0818] 114
[0819] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.1 Hz),
2.82 (3H, s), 3.36 and 3.75 (2H, ABq, J=18.5 Hz), 4.72 (2H, t,
J=6.5 Hz), 4.99 (1H, q, J=7.1 Hz), 5.36 (1H, d, J=4.8 Hz), 5.40 and
5.86 (2H, ABq, J=14.9 Hz), 5.94 (1H, d, J=4.8 Hz), 8.09 (1H, d,
J=6.8 Hz), 8.83 (1H, d, J=6.8 Hz), 9.06 (1H, s).
[0820] IR (KBr) cm.sup.-1: 3370, 3174, 1771, 1667, 1606, 1541,
1504, 1449, 1399, 1360, 1312, 1281, 1184, 1113, 1067, 1035.
[0821] MS(FAB): 679.sup.+(M+H).sup.+.
[0822] Elementary Analysis as
C.sub.25H.sub.27ClN.sub.10O.sub.7S.sub.2.mul-
tidot.4.0H.sub.2O.
[0823] Calculated: C, 39.97; H, 4.70; N, 18.65; Cl, 4.72; S, 8.54
(%). Found: C, 40.02; H, 4.64; N, 18.79; Cl, 4.60; S, 8.31 (%).
EXAMPLE 66
[0824] 115
[0825] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.1 Hz),
3.29-3.45 (6H, m), 3.69 (1H, d, J=18.3 Hz), 4.04 (2H, t, J=6.2 Hz),
4.98 (1H, q, J=7.1 Hz), 5.28-5.35 (2H, m), 5.70 (1H, s), 5.93 (1H,
d, J=4.8 Hz), 7.68 (1H, d, J=4.6 Hz), 8.45 (1H, dd, J=1.2, 4.6 Hz),
8.73 (1H, d, J=1.2 Hz).
[0826] IR (KBr) cm.sup.-1: 3397, 1772, 1623, 1578, 1540, 1508,
1446, 1397, 1330, 1247, 1190, 1151, 1121, 1066, 1034.
[0827] MS(FAB): 679.sup.+(M+H).sup.+.
[0828] Elementary Analysis as
C.sub.25H.sub.27ClN.sub.10O.sub.7S.sub.2.mul-
tidot.4.3H.sub.2O.
[0829] Calculated: C, 39.69; H, 4.74; N, 18.51; Cl, 4.69; S, 8.48
(%). Found: C, 39.77; H, 4.70; N, 18.43; Cl, 4.59; S, 8.48 (%).
EXAMPLE 67
[0830] 116
[0831] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.54 (3H, d, J=7.1 Hz),
2.80 (3H, s), 3.29 and 3.66 (2H, ABq, J=18.3 Hz), 3.41 (2H, t,
J=5.8 Hz), 3.89 (2H, t, J=5.8 Hz), 4.96 (1H, q, J=7.1 Hz),
5.27-5.33 (2H, m), 5.61 (1H, d, J=14.8 Hz), 5.93 (1H, d, J=4.8 Hz),
7.67 (1H, d, J=6.8 Hz), 8.43 (1H, d, J=6.8 Hz), 8.71 (1H,s).
[0832] IR (KBr) cm.sup.-1: 3388, 1773, 1626, 1540, 1477, 1395,
1361, 1238, 1186, 1152, 1120, 1065, 1035.
[0833] MS(FAB): 679.sup.+(M+H).sup.+.
[0834] Elementary Analysis as
C.sub.25H.sub.27ClN.sub.10O.sub.7S.sub.2.mul-
tidot.3.7H.sub.2O.
[0835] Calculated: C, 40.26; H, 4.65; N, 18.78; Cl, 4.75; S, 8.60
(%). Found: C, 40.23; H, 4.60; N, 18.76; Cl, 4.79; S, 8.51 (%).
EXAMPLE 68
[0836] 117
[0837] .sup.1H-NMR (D.sub.2O) .delta.: 1.42 (3H, d, J=6.9 Hz), 2.74
(3H, s), 3.17 (1H, d, J=18.0 Hz), 3.56-3.61 (3H, m), 4.61-4.76 (3H,
m), 5.23-5.31 (2H, m), 5.54 (1H, d, J=14.7 Hz), 5.56 (1H, d, J=4.5
Hz), 7.12 (1H, d, J=3.4 Hz), 7.80 (1H, d, J=3.4 Hz), 7.99 (1H, d,
J=7.0 Hz), 8.52 (1H, d, J=7.0 Hz), 9.086 (1H, s).
[0838] IR (KBr) cm.sup.-1: 3398, 2452, 1773, 1604, 1540, 1514,
1494, 1448, 1395, 1363, 1286, 1223, 1187, 1119, 1065, 1034.
[0839] MS(FAB): 663.sup.+(M+H).sup.+.
[0840] Elementary Analysis as
C.sub.26H.sub.27ClN.sub.8O.sub.7S.sub.2 4.0H.sub.2O.
[0841] Calculated: C, 42.48; H, 4.80; N, 15.24; Cl, 4.82; S, 8.72
(%). Found: C, 42.45; H, 4.57; N, 15.20; Cl, 4.86; S, 8.70 (%).
EXAMPLE 69
[0842] 118
[0843] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39 (3H, d, J=7.0 Hz),
3.02 and 3.31 (2H ABq, J=17.7 Hz), 4.57 (1H, q, J=7.0 Hz), 5.05
(1H, d, J=4.9 Hz), 5.22 and 5.35 (2H, ABq, J=14.4 Hz), 5.75 (1H,
dd, J=4.9, 9.0 Hz), 5.87 (1H, s), 6.84 (1H, t-like), 7.39 (2H,
brs), 7.49 (1H, d, J=7.5 Hz), 7.82 (1H, brs), 8.09 (1H, d, J=6.6
Hz), 9.86 (1H, brs), 12.9 (1H, brs).
[0844] IR (KBr) cm.sup.-1: 3338, 3198, 1773, 1640, 1581, 1540,
1497, 1427, 1364, 1329, 1285, 1239, 1192, 1159, 1099, 1034.
[0845] MS(FAB): 621.sup.+(M+H).sup.+.
[0846] Elementary Analysis as
C.sub.23H.sub.21ClN.sub.8O.sub.7S.sub.2 2.9H.sub.2O.
[0847] Calculated: C, 41.03; H, 4.01; N, 16.64; Cl, 5.27; S, 9.52
(%). Found: C, 41.01; H, 3.90; N, 16.64; Cl, 5.37; S, 9.49 (%).
EXAMPLE 70
[0848] 119
[0849] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.36 (3H, d, J=7.1 Hz),
3.01 and 3.47 (2H, ABq, J=17.7 Hz), 3.60 (3H, s), 4.53 (1H, q,
J=7.1 Hz), 4.90 and 5.50 (2H, ABq, J=13.7 Hz), 5.04 (1H, d, J=4.9
Hz), 5.69 (1H, dd, J=4.9, 9.0 Hz), 7.40 (2H, brs), 7.51 (1H, d,
J=6.8 Hz), 8.14 (2H, brs), 8.82 (1H, d, J=6.8 Hz), 9.13 (1H, brs),
9.68 (1H, brs).
[0850] IR (KBr) cm.sup.-1: 3354, 3190, 1774, 1658, 1557, 1485,
1467, 1389, 1347, 1231, 1162, 1094, 1066, 1035.
[0851] MS(FAB): 636.sup.+(M+H).sup.+.
[0852] Elementary Analysis as
C.sub.23H.sub.22ClN.sub.9O.sub.7S.sub.2.mult- idot.3.2H.sub.2O.
[0853] Calculated: C, 39.82; H, 4.13; N, 18.17; Cl, 5.11; S, 9.24
(%). Found: C, 39.85; H, 4.07; N, 18.08; Cl, 5.02; S, 9.12 (%).
EXAMPLE 71
[0854] 120
[0855] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.54 (3H, d, J=7.2 Hz),
3.33 and 3.59 (2H ABq, J=18.5 Hz), 3.67 (3H, s), 4.99 (1H, q, J=7.2
Hz), 5.29 (1H, d, J=4.8 Hz), 5.22 and 5.65 (2H, ABq, J=15.2 Hz),
5.91 (1H, d, J=4.8 Hz), 7.33 (1H, dd, J=6.5, 7.8 Hz), 7.91 (1H, d,
J=7.8 Hz), 8.10 (1H, d, J=6.5 Hz).
[0856] IR (KBr) cm.sup.-1: 3455, 3351, 3288, 3041, 2949, 2899,
1746, 1699, 1671, 1651, 1625, 1606, 1579, 1533, 1494, 1462, 1447,
1422, 1404, 1364, 1354, 1303, 1275, 1254, 1227, 1209, 1189, 1173,
1155, 1140, 1091, 1076, 1064, 1026.
[0857] MS(FAB): 636.sup.+(M+H).sup.+.
[0858] Elementary Analysis as
C.sub.23H.sub.22ClN.sub.9O.sub.7S.sub.2.mult- idot.2.5H.sub.2O.
[0859] Calculated: C, 42.82; H, 3.59; N, 19.54; Cl, 5.50; S, 9.94
(%). Found: C, 42.84; H, 3.55; N, 19.51; Cl, 5.43; S, 10.00
(%).
EXAMPLE 72
[0860] 121
[0861] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=7.1 Hz),
3.00 and 3.49 (2H, ABq, J=17.7 Hz), 4.54 (1H, q, J=7.1 Hz), 5.02
and 5.63 (2H, ABq, J=13.7 Hz), 5.07 (1H, d, J=5.0 Hz), 5.72 (1H,
dd, J=5.0, 8.7 Hz), 7.41 (2H, brs), 8.12 (1H, d, J=7.1 Hz), 8.72
(2H, brs), 9.10 (1H, d, J=7.1 Hz), 9.45 (1H, brs), 9.55 (1H, d,
J=8.7 Hz).
[0862] IR (KBr) cm.sup.-1: 3385, 1776, 1692, 1617, 1538, 1492,
1363, 1287, 1223, 1188, 1150, 1103, 1066, 1036.
[0863] MS(FAB): 623.sup.+(M+H).sup.+.
[0864] Elementary Analysis as
C.sub.22H.sub.19ClN.sub.8O.sub.8S.sub.2.mult- idot.2.9H.sub.2O.
[0865] Calculated: C, 39.13; H, 3.70; N, 16.59; Cl, 5.25; S, 9.50
(%). Found: C, 39.04; H, 3.55; N, 16.69; Cl, 5.12; S, 9.52 (%).
EXAMPLE 73
[0866] 122
[0867] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.38 (3H, d, J=7.0 Hz),
3.15 and 3.50 (2H, ABq, J=17.6 Hz), 4.55 (1H, q, J=7.0 Hz), 5.07
(1H, d, J=5.1 Hz), 5.11 (1H, d, J=13.2 Hz), 5.65-5.74 (2H, m), 7.41
(2H, brs), 8.24-8.31 (1H, m), 8.62-8.68 (1H, m), 9.46 (1H, d, J=6.0
Hz), 9.52 (1H, d, J=8.7 Hz), 9.89 (1H, brs).
[0868] IR (KBr) cm.sup.-1: 3411, 3068, 2943, 1778, 1673, 1616,
1538, 1503, 1446, 1390, 1345, 1275, 1189, 1137, 1097, 1065,
1035.
[0869] MS(FAB): 585.sup.+(M+H).sup.+.
[0870] Elementary Analysis as
C.sub.21H.sub.18ClFN.sub.6O.sub.7S.sub.2.mul-
tidot.2.9H.sub.2O.
[0871] Calculated: C, 39.58; H, 3.76; N, 13.19; Cl, 5.56; S, 10.06
(%). Found: C, 39.52; H, 3.59; N, 13.24; Cl, 5.65; S, 10.25
(%).
EXAMPLE 74
[0872] 123
[0873] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.54 (3H, d, J=7.1 Hz),
2.78 (3H, s), 3.37 (1H, d, J=18.3 Hz), 3.54-3.62 (3H, m), 4.57 (2H,
t, J=6.5 Hz), 4.98 (1H, q, J=7.1 Hz), 5.27 (1H, d, J=4.8 Hz), 5.49
and 5.71 (2H, ABq, J=15.2 Hz), 5.91 (1H, d, J=4.8 Hz), 7.34
(1H,t-like), 8.00 (1H, d, J=7.8 Hz), 8.17 (1H, d, J=6.6 Hz).
[0874] IR (KBr) cm.sup.-1: 3398, 2451, 1771, 1666, 1603, 1562,
1493, 1396, 1362, 1315, 1387, 1224, 1165, 1090, 1034.
[0875] MS(FAB): 679.sup.+(M+H).sup.+.
[0876] Elementary Analysis as
C.sub.25H.sub.27ClN.sub.10O.sub.7S.sub.2.mul-
tidot.3.6H.sub.2O.
[0877] Calculated: C, 40.36; H, 4.63; N, 18.83; Cl, 4.77; S, 8.62
(%). Found: C, 40.32; H, 4.68; N, 18.84; Cl, 4.87; S, 8.77 (%).
EXAMPLE 75
[0878] 124
[0879] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.54 (3H, d, J=7.1 Hz),
2.64 (3H, s), 3.25 and 3.45 (2H ABq, J=18.3 Hz), 3.38 (2H, t, J=5.9
Hz), 3.76 (2H, t, J=5.9 Hz), 4.98 (1H, q, J=7.1 Hz), 5.26 (1H, d,
J=4.8 Hz), 5.39 and 5.48 (2H, ABq, J=15.5 Hz), 5.89 (1H, d, J=4.8
Hz), 7.10 (1H, t-like), 7.73 (1H, d, J=7.8 Hz), 7.94 (1H, d, J=6.6
Hz).
[0880] IR (KBr) cm.sup.-1: 3389, 1771, 1590, 1540, 1428, 1395,
1360, 1317, 1284, 1192, 1158, 1113, 1058, 1033.
[0881] MS(FAB): 678.sup.+(M+H).sup.+.
[0882] Elementary Analysis as
C.sub.26H.sub.28ClN.sub.9O.sub.7S.sub.2 3.3H.sub.2O.
[0883] Calculated: C, 42.34; H, 4.73; N, 17.09; Cl, 4.81; S, 8.69
(%). Found: C, 42.11; H, 4.67; N, 17.00; Cl, 4.94; S, 9.09 (%).
EXAMPLE 76
[0884] 125
[0885] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.40 (3H, d, J=7.1 Hz),
2.26 (3H,s), 3.12 and 3.45 (2H, ABq, J=17.7 Hz), 4.59 (1H, q, J=7.1
Hz), 5.20 (1H, d, J=4.9 Hz), 5.78 (1H, dd, J=4.9, 9.2 Hz), 7.41
(2H, brs), 8.12 (1H, d, J=6.3 Hz), 8.39 (1H, brs), 8.47 (1H, d,
J=6.3 Hz), 9.60 (1H, d, J=9.2 Hz), 10.05 (1H, brs).
[0886] IR (KBr) cm.sup.-1: 3330, 1777, 1674, 1623, 1529, 1475,
1379, 1314, 1230, 1141, 1102, 1066, 1036.
[0887] MS(ESI): 640.sup.+(M+H).sup.+.
[0888] Elementary Analysis as
C.sub.23H.sub.22ClN.sub.7O.sub.9S.sub.2.mult- idot.2.8H.sub.2O.
[0889] Calculated: C, 40.01; H, 4.03; N, 14.20; Cl, 5.13; S, 9.29
(%). Found: C, 39.92; H, 3.90; N, 14.32; Cl, 5.27; S, 9.31 (%).
EXAMPLE 77
[0890] 126
[0891] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.35 (3H, d, J=6.9 Hz),
3.05 and 3.48 (2H, ABq, J=17.6 Hz), 4.53 (1H, q, J=6.9 Hz), 5.06
(1H, d, J=4.8 Hz), 5.13 (1H, d, J=13.8 Hz), 5.64-5.73 (2H, m), 7.40
(2H, brs), 7.66 (1H, s), 7.87 (1H, brs), 7.94 (1H, d, J=6.9 Hz),
8.51 (1H, brs), 8.97 (1H, d, J=6.9 Hz), 9.62 (1H, brs), 9.81 (1H,
brs).
[0892] IR (KBr) cm.sup.-1: 3327, 3195, 1775, 1677, 1613, 1540,
1375, 1335, 1240, 1182, 1152, 1116, 1066, 1036.
[0893] MS(ESI): 649.sup.+(M+H).sup.+.
[0894] Elementary Analysis as
C.sub.24H.sub.21ClN.sub.8O.sub.8S.sub.2.mult- idot.2.4H.sub.2O.
[0895] Calculated: C, 41.64; H, 3.76; N, 16.19; Cl, 5.12; S, 9.26
(%). Found: C, 41.70; H, 3.71; N, 16.24; Cl, 5.00; S, 9.063
(%).
EXAMPLE 78
[0896] 127
[0897] .sup.1H-NMR (D.sub.2O) .delta.: 1.43 (3H, d, J=7.1 Hz), 2.39
(2H, quint. J=7.8 Hz), 2.72 (3H, s), 3.15 (2H, t, J=7.8 Hz), 3.26
and 3.62 (2H, ABq, J=18.0 Hz), 4.59-4.69 (3H, m), 5.23 (1H, d,
J=4.8 Hz), 5.62 (1H, d, J=14.7 Hz), 5.70-5.75 (2H, m), 7.89 (1H,dd,
J=6.3, 8.3 Hz), 8.78 (1H, d, J=8.3 Hz), 8.86 (1H, brs), 8.88 (1H,
d, J=6.3 Hz).
[0898] IR (KBr) cm.sup.-1: 3397, 2464, 1773, 1602, 1541, 1490,
1463, 1389, 1313, 1287, 1237, 1187, 1159, 1115, 1064, 1034.
[0899] MS(ESI): 678.sup.+(M+H).sup.+.
[0900] Elementary Analysis as
C.sub.26H.sub.28ClN.sub.9O.sub.7S.sub.2.mult- idot.3.7H.sub.2O.
[0901] Calculated: C, 41.93; H, 4.79; N, 16.93; Cl, 4.76; S, 8.61
(%). Found: C, 41.93; H, 4.74; N, 16.89; Cl, 4.53; S, 8.58 (%).
EXAMPLE 79
[0902] 128
[0903] .sup.1H-NMR (D.sub.2O) .delta.: 1.44 (3H, d, J=7.0 Hz), 2.20
(2H, m), 2.70 (3H, s), 3.12 (2H, m), 3.24 and 3.50 (2H, ABq, J=17.9
Hz), 4.22 (2H, t, J=7.1 Hz), 4.55 (1H, q, J=7.0 Hz), 5.18 (1H, d,
J=4.8 Hz), 5.25 and 5.56 (2H, ABq, J=14.7 Hz), 5.84 (1H, d, J=4.8
Hz), 7.30 (1H, t-like), 7.89 (1H, d, J=7.8 Hz), 8.12 (1H, d, J=6.6
Hz).
[0904] IR (KBr) cm.sup.-1: 3363, 3181, 1772, 1651, 1600, 1565,
1494, 1394, 1364, 1315, 1288, 1223, 1163, 1091, 1034.
[0905] MS(ESI): 693.sup.+(M+H).sup.+.
[0906] Elementary Analysis as
C.sub.26H.sub.29ClN.sub.10O.sub.7S.sub.2.mul-
tidot.2.9H.sub.2O.
[0907] Calculated: C, 41.89; H, 4.71; N, 18.79; Cl, 4.76; S, 8.60
(%). Found: C, 41.93; H, 4.73; N, 18.81; Cl, 4.51; S, 8.51 (%).
EXAMPLE 80
[0908] 129
[0909] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.1 Hz),
3.35 and 3.63 (2H ABq, J=18.9 Hz), 5.39 (1H, d, J=5.1 Hz), 5.98
(1H, d, J=5.1 Hz), 6.03 and 6.24 (2H, ABq, J=15.6 Hz), 8.40 (1H,
dd, J=5.7, 8.7 Hz), 9.04 (1H, d, J=9.3 Hz), 9.29 (1H, d, J=8.7 Hz),
9.17-9.20 (2H, m).
[0910] IR (KBr) cm.sup.-1: 3411, 3197, 1778, 1675, 1617, 1538,
1521, 1456, 1376, 1339, 1285, 1230, 1189, 1152, 1098, 1066,
1035.
[0911] MS(ESI): 618.sup.+(M+H).sup.+.
[0912] Elementary Analysis as
C.sub.24H.sub.20ClN.sub.7O.sub.7S.sub.2.mult- idot.3.0H.sub.2O.
[0913] Calculated: C, 42.89; H, 3.90; N, 14.59; Cl, 5.28; S, 9.54
(%). Found: C, 42.91; H, 3.97; N, 12.66; Cl, 5.18; S, 9.51 (%).
EXAMPLE 81
[0914] 130
[0915] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.2 Hz),
2.80 (3H, s), 3.38 and 3.77 (2H, ABq, J=18.9 Hz), 3.38 (3H, s),
3.45 (3H, s), 3.64 (2H, t, J=5.7 Hz), 4.76 (2H, t, J=5.7 Hz), 4.99
(1H, q, J=7.2 Hz), 5.37 (1H, d, J=4.8 Hz), 5.42 and 5.88 (2H, ABq,
J=14.6 Hz), 5.95 (1H, d, J=4.8 Hz), 8.13 (1H, d, J=7.0 Hz), 8.68
(1H, brs), 8.84 (1H, dd, J=1.2, 7.0 Hz), 9.14 (1H, d, J=1.2
Hz).
[0916] IR (KBr) cm.sup.-1: 3406, 1773, 1632, 1535, 1497, 1421,
1389, 1352, 1308, 1237, 1183, 1114, 1065, 1034.
[0917] MS(FAB): 734.sup.+(M+H).sup.+.
[0918] Elementary Analysis as
C.sub.28H.sub.32ClN.sub.11O.sub.7S.sub.2.mul-
tidot.5.5H.sub.2O.
[0919] Calculated: C, 40.36; H, 5.20; N, 18.49; Cl, 4.25; S, 7.70
(%). Found: C, 40.38; H, 5.03; N, 18.36; Cl, 4.52; S, 7.89 (%).
EXAMPLE 82
[0920] 131
[0921] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.44 (3H, d, J=6.9 Hz),
2.39 (2H, m), 2.73 (3H, s), 3.23 (2H, m), 3.30 and 3.68 (2H, ABq,
J=18.0 Hz), 4.59-4.69 (3H, m), 5.24 (1H, d, J=5.0 Hz), 5.67 and
5.93 (2H, ABq, J=14.7 Hz), 5.88 (1H, d, J=5.0 Hz), 8.09 (1H,dd,
J=8.2, 6.1 Hz), 8.99 (1H, d, J=8.2 Hz), 9.12(1H, d, J=6.1 Hz).
[0922] IR (KBr) cm.sup.-1: 3403, 2467, 1776, 1604, 1540, 1482,
1458, 1437, 1394, 1352, 1317, 1269, 1195, 1155, 1121, 1096, 1065,
1034.
[0923] MS(FAB): 7462.sup.+(M+H).sup.+.
[0924] Elementary Analysis as
C.sub.27H.sub.27ClF.sub.3N.sub.9O.sub.7S.sub-
.2.multidot.3.7H.sub.2O.
[0925] Calculated: C, 39.90; H, 4.27; N, 15.51; Cl, 4.36; S, 7.89
(%). Found: C, 39.98; H, 4.33; N, 15.51; Cl, 4.12; S, 7.73 (%).
EXAMPLE 83
[0926] 132
[0927] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.56 (3H, d, J=6.9 Hz),
2.50 (2H, m), 2.77 (3H, s), 3.33 (2H, m), 3.59 and 3.72 (2H, ABq,
J=18.3 Hz), 4.93-5.04 (3H, m), 5.27 (1H, d, J=5.1 Hz), 5.77 and
6.28 (2H, ABq, J=14.9 Hz), 5.92 (1H, d, J=5.1 Hz), 8.05 (1H,dd,
J=8.4, 6.3 Hz), 8.99 (1H, d, J=8.4 Hz), 9.03(1H, d, J=6.3 Hz).
[0928] IR (KBr) cm.sup.-1: 3400, 1776, 1604, 1539, 1450, 1392,
1350, 1321, 1287, 1224, 1159, 1063, 1033.
[0929] MS(FAB): 794.sup.+(M+H).sup.+.
[0930] Elementary Analysis as
C.sub.27H.sub.27Cl.sub.4N.sub.9O.sub.7S.sub.-
2.multidot.3.3H.sub.2O.
[0931] Calculated: C, 37.93; H, 3.96; N, 14.74; Cl, 16.59; S, 7.50
(%). Found: C, 38.26; H, 4.00; N, 14.96; Cl, 15.25; S, 7.46
(%).
EXAMPLE 84
[0932] 133
[0933] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=7.1 Hz),
3.02 and 3.48 (2H, ABq, J=17.9 Hz), 4.54 (1H, q, J=7.1 Hz), 4.90
and 5.50 (2H, ABq, J=13.5 Hz), 5.05 (1H, d, J=4.8 Hz), 5.70 (1H,
dd, J=4.8, 8.7 Hz), 7.41 (2H, brs), 7.69 (1H, d, J=6.8 Hz), 9.01
(1H, d, J=6.8 Hz), 9.33 (2H, brs), 9.58 (2H, brs).
[0934] IR (KBr) cm.sup.-1: 3393, 1776, 1687, 1615, 1559, 1513,
1484, 1377, 1326, 1284, 1213, 1188, 1154, 1106, 1066, 1034.
[0935] MS(FAB): 623.sup.+(M+H).sup.+.
[0936] Elementary Analysis as
C.sub.22H.sub.19ClN.sub.8O.sub.8S.sub.2 2.7H.sub.2O.
[0937] Calculated: C, 39.34; H, 3.66; N, 16.68; Cl, 5.28; S, 9.55
(%). Found: C, 39.35; H, 3.67; N, 16.61; Cl, 5.26; S, 9.48 (%).
EXAMPLE 85
[0938] 134
[0939] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39 (3H, d, J=6.9 Hz),
2.95 and 3.42 (2H ABq, J=17.4 Hz), 4.55 (1H, q, J=6.9 Hz), 4.73 and
5.21 (2H, ABq, J=13.8 Hz), 5.13 (1H, d, J=4.8 Hz), 5.71 (1H, dd,
J=4.8, 8.7 Hz), 6.73 (1H, d, J=6.9 Hz), 7.40 (2H, brs), 7.99 (1H,
d, J=6.9 Hz), 8.27 (1H, brs), 9.79 (1H, brs).
[0940] IR (KBr) cm.sup.-1: 3343, 3202, 1776, 1644, 1546, 1446,
1370, 1309, 1258, 1179, 1147, 1065, 1036.
[0941] MS(FAB): 598.sup.+(M+H).sup.+.
[0942] Elementary Analysis as
C.sub.21H.sub.20ClN.sub.7O.sub.7S.sub.2.mult- idot.2.6H.sub.2O.
[0943] Calculated: C, 39.11; H, 3.949; N, 15.20; Cl, 5.50; S, 9.94
(%). Found: C, 39.18; H, 3.74; N, 15.14; Cl, 5.38; S, 9.82 (%).
EXAMPLE 86
[0944] 135
[0945] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.44 (3H, d, J=7.1 Hz),
2.80 (3H, s), 3.20 and 3.53 (2H, ABq, J=17.9 Hz), 3.75 (2H, t,
J=5.5 Hz), 4.66 (1H, q, J=7.1 Hz), 5.03 (2H, t, J=5.5 Hz), 5.23
(1H, d, J=5.0 Hz), 5.79 (2H, s), 5.88 (1H, d, J=5.0 Hz), 8.07
(1H,dd, J=8.7, 5.8 Hz), 8.82 (1H, s), 8.96 (1H, d, J=8.7 Hz), 9.05
(1H, d, J=5.8 Hz).
[0946] IR (KBr) cm.sup.-1: 3408, 1773, 1604, 1540, 1476, 1447,
1394, 1352, 1316, 1289, 1222, 1187, 1159, 1080, 1034.
[0947] MS(FAB): 664.sup.+(M+H).sup.+.
[0948] Elementary Analysis as
C.sub.2526.sub.9ClN.sub.9O.sub.7S.sub.2.mult- idot.3.0H.sub.2O.
[0949] Calculated: C, 41.81; H, 4.49; N, 17.55; Cl, 4.94; S, 8.93
(%). Found: C, 41.86; H, 4.45; N, 17.66; Cl, 4.81; S, 8.71 (%).
EXAMPLE 87
[0950] 136
[0951] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.44 (3H, d, J=7.1 Hz),
2.78 (3H, s), 3.11 and 3.52 (2H, ABq, J=17.9 Hz), 3.78 (2H, t,
J=5.6 Hz), 4.66 (1H, q, J=7.1 Hz), 5.09 (2H, t, J=5.6 Hz), 5.23
(1H, d, J=4.8 Hz), 5.63 and 5.81 (2H, ABq, J=15.2 Hz), 5.85 (1H, d,
J=4.8 Hz), 7.95 (1H,dd, J=9.0, 5.4 Hz), 8.97 (1H, d, J=9.0 Hz),
9.07 (1H, d, J=5.4 Hz), 9.21 (1H, brs).
[0952] IR (KBr) cm.sup.-1: 3408, 1773, 1603, 1540, 1476, 1447,
1394, 1352, 1316, 1289, 1223, 1187, 1159, 1080, 1034.
[0953] MS(FAB): 664.sup.+(M+H).sup.+.
[0954] Elementary Analysis as
C.sub.25H.sub.26ClN.sub.9O.sub.7S.sub.2.mult- idot.3.1H.sub.2O.
[0955] Calculated: C, 41.71; H, 4.51; N, 17.51; Cl, 4.92; S, 8.91
(%). Found: C, 41.75; H, 4.39; N, 17.57; Cl, 4.64; S, 8.71 (%).
EXAMPLE 88
[0956] 137
[0957] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.2 Hz),
2.85 (3H, s), 3.53 and 3.80 (2H, ABq, J=18.0 Hz), 3.91 (2H, t,
J=6.0 Hz), 5.34 (1H, d, J=4.8 Hz), 5.40 (2H, t, J=6.0 Hz), 5.96
(1H, d, J=4.8 Hz), 6.07 and 6.29 (2H, ABq, J=15.0 Hz), 8.28 (1H,dd,
J=5.4, 8.4 Hz), 9.25 (1H, d, J=8.4 Hz), 9.34(1H, d, J=5.4 Hz).
[0958] IR (KBr) cm.sup.-1: 3408, 2448, 1774, 1606, 1539, 1465,
1393, 1348, 1283, 1188, 1155, 1093, 1065, 1034.
[0959] MS(ESI): 655(M+H).sup.+.
[0960] Elementary Analysis as
C.sub.24H.sub.25ClN.sub.10O.sub.7S.sub.2.mul-
tidot.3.6H.sub.2O.
[0961] Calculated: C, 39.49; H, 4.45; N, 19.19; Cl, 4.86; S, 8.79
(%). Found: C, 39.50; H, 4.42; N, 19.21; Cl, 4.80; S, 8.67 (%).
EXAMPLE 89
[0962] 138
[0963] .sup.1H-NMR (D.sub.2O) .delta.: 1.44 (3H, d, J=7.0 Hz), 2.22
(2H, m), 2.70 (3H, s), 3.08 (2H, m), 3.27 and 3.51 (2H, ABq, J=18.0
Hz), 3.36 (6H, s), 4.36 (2H, t,-like), 5.16 (1H, d, J=4.5 Hz), 5.22
and 5.67 (2H, ABq, J=14.7 Hz), 5.83 (1H, d, J=4.5 Hz), 7.26 (1H,
t-like), 7.85 (1H, d, J=7.8 Hz), 8.08 (1H, d, J=6.6 Hz).
[0964] IR (KBr) cm.sup.-1: 3399, 1773, 1629, 1584, 1541, 1501,
1419, 1350, 1320, 1226, 1167, 1137, 1064, 1033.
[0965] MS(FAB): 721.sup.+(M+H).sup.+.
[0966] Elementary Analysis as
C.sub.28H.sub.33ClN.sub.10O.sub.7S.sub.2.mul-
tidot.3.0H.sub.2O.
[0967] Calculated: C, 43.38; H, 5.07; N, 18.07; Cl, 4.57; S, 8.27
(%). Found: C, 43.43; H, 5.05; N, 18.07; Cl, 4.36; S, 8.10 (%).
EXAMPLE 90
[0968] 139
[0969] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.56 (3H, d, J=7.5 Hz),
2.22 (2H, m), 2.72 (3H, s), 3.12-3.18 (5H, m), 3.46 and 3.60 (2H,
ABq, J=18.5 Hz), 4.22 (2H, t, J=7.5 Hz), 5.01 (1H, q, J=7.5 Hz),
5.27 (1H, d, J=4.8 Hz), 5.27 (1H, d, J=4.8 Hz), 5.43 (1H, d, J=15.0
Hz), 5.85-5.91 (2H, m), 7.32 (1H, dd, J=6.7, 7.6 Hz), 7.92 (1H, d,
J=7.6 Hz), 8.10 (1H, d, J=6.7 Hz).
[0970] IR (KBr) cm.sup.-1: 3398, 1773, 1642, 1596, 1541, 1496,
1412, 1392, 1366, 1316, 1222, 1165, 1139, 1099, 1064, 1034.
[0971] MS(ESI): 707.sup.+(M+H).sup.+.
[0972] Elementary Analysis as
C.sub.27H.sub.31ClN.sub.10O.sub.7S.sub.2.mul-
tidot.3.5H.sub.2O.
[0973] Calculated: C, 42.10; H, 4.97; N, 18.18; Cl, 4.60; S, 8.33
(%). Found: C, 42.09; H, 4.97; N, 18.19; Cl, 4.44; S, 8.18 (%).
EXAMPLE 91
[0974] 140
[0975] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.2 Hz),
2.33 (2H, d-like), 2.61 (2H, q-like), 3.25-3.39 (3H, m), 3.60 (1H,
d, J=18.3 Hz), 3.72 (2H, d-like), 4.99 (1H, q, J=7.2 Hz), 5.29 (1H,
d, J=4.9 Hz), 5.50 and 5.69 (2H, ABq, J=15.0 Hz), 5.92 (1H, d,
J=4.9 Hz), 7.33 (1H, t-like), 8.14 (2H, m).
[0976] IR (KBr) cm.sup.-1: 3380, 3182, 1772, 1601, 1555, 1491,
1440, 1395, 1362, 1317, 1287, 1225, 1169, 1092, 1033.
[0977] MS(ESI): 705.sup.+(M+H).sup.+.
[0978] Elementary Analysis as
C.sub.27H.sub.29ClN.sub.10O.sub.7S.sub.2.mul-
tidot.4.5H.sub.2O.
[0979] Calculated: C, 41.25; H, 4.87; N, 17.81; Cl, 4.51; S, 8.16
(%). Found: C, 41.38; H, 4.79; N, 17.71; Cl, 4.19; S, 7.50 (%).
EXAMPLE 92
[0980] 141
[0981] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.36 (3H, d, J=7.1 Hz),
1.55 (3H, t, J=7.3 Hz), 2.38 (2H, d-like), 2.62-2.72 (2H,m),
3.27-3.35 (2H m), 3.44 (1H, d., J=18.6 Hz), 3.68-3.74 (3H, m), 4.37
(2H, q, J=7.3 Hz), 4.99 (1H, q, J=7.1 Hz), 5.31 (1H, d, J=5.1 Hz),
5.73 (1H, d, J=15.1 Hz), 5.90-5.95 (2H, m), 7.74 (1H, dd, J=6.6,
7.9 Hz), 8.63 (1H, d, J=6.6 Hz), 8.69 (1H, d, J=7.9 Hz).
[0982] IR (KBr) cm.sup.-1: 3409, 2982, 2527, 1775, 1607, 1538,
1468, 1385, 1283, 1223, 1174, 1094, 1033.
[0983] MS(ESI): 777.sup.+(M+H).sup.+.
[0984] Elementary Analysis as
C.sub.30H.sub.33ClN.sub.10O.sub.9S.sub.2.mul-
tidot.4.8H.sub.2O.
[0985] Calculated: C, 41.72; H, 4.97; N, 16.22; Cl, 4.10; S, 7.43
(%). Found: C, 41.68; H, 4.86; N, 16.33; Cl, 4.08; S, 7.46 (%).
EXAMPLE 93
[0986] 142
[0987] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.56 (3H, d, J=5.4 Hz),
2.38 (2H, m), 2.74 (3H, s), 3.19 (2H, m), 3.54 (2H, m), 4.96(3H,
m), 5.19 (1H, brs), 5.62-6.32 (2H, m), 5.87 (1H, brs), 7.99 (1H,
m), 8.93 (1H, d, J=7.5 Hz), 9.01(1H, d, J=5.7 Hz).
[0988] IR (KBr) cm.sup.-1: 3399, 1771, 1698, 1667, 1602, 1540,
1460, 1394, 1358, 1327, 1287, 1221, 1187, 1152, 1082, 1061,
1034.
[0989] MS(ESI): 721.sup.+(M+H.sup.+).
[0990] Elementary Analysis as
C.sub.27H.sub.29ClN.sub.10O.sub.8S.sub.2.mul-
tidot.5.0H.sub.2O.
[0991] Calculated: C, 39.97; H, 4.85; N, 17.27; Cl, 4.37; S, 7.91
(%). Found: C, 39.88; H, 4.45; N, 17.07; Cl, 4.40; S, 7.99 (%).
EXAMPLE 94
[0992] 143
[0993] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.1 Hz),
2.79 (3H, s), 3.35 and 3.54 (2H, ABq, J=18.5 Hz), 3.54 (2H, t,
J=5.6 Hz), 4.44 (2H, t, J=5.6 Hz), 4.99 (1H, q, J=7.1 Hz), 5.36
(1H, d, J=5.0 Hz), 5.31 and 5.79 (2H, ABq, J=14.7 Hz), 5.94 (1H, d,
J=5.0 Hz), 7.79 (1H, d, J=6.7 Hz), 8.65 (1H, dd, J=1.2, 6.7 Hz),
8.72 (1H, brs).
[0994] IR (KBr) cm.sup.-1: 3395, 3086, 1748, 1660, 1611, 1528,
1448, 1396, 1353, 1313, 1288, 1212, 1188, 1156, 1136, 1111, 1106,
1035.
[0995] MS(ESI): 680.sup.+(M+H).sup.+.
[0996] Elementary Analysis as
C.sub.25H.sub.26ClN.sub.9O.sub.8S.sub.2.mult- idot.3.4H.sub.2O.
[0997] Calculated: C, 40.50; H, 4.46; N, 17.00; Cl, 4.78; S, 8.56
(%). Found: C, 40.73; H, 4.45; N, 17.10; Cl, 4.65; S, 8.35 (%).
EXAMPLE 95
[0998] 144
[0999] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.56 (3H, d, J=7.1 Hz),
2.79 (3H, s), 3.31 and 3.66 (2H, ABq, J=18.3 Hz), 3.40 (2H, t,
J=5.9 Hz), 3.85 (2H, t, J=5.9 Hz), 4.96-5.03 (2H, m), 5.33 (1H, d,
J=5.1 Hz), 5.41 (1H, d, J=14.7 Hz), 5.93 (1H, d, J=5.1 Hz), 6.95
(1H, d, J=7.2 Hz), 7.71 (1H, d, J=1.8 Hz), 8.05 (1H, dd, J=1.8, 7.2
Hz).
[1000] IR (KBr) cm.sup.-1: 3368, 1773, 1627, 1556, 1455, 1395,
1349, 1321, 1287, 1190, 1158, 1093, 1065, 1034.
[1001] MS(ESI): 654.sup.+(M+H).sup.+.
[1002] Elementary Analysis as
C.sub.24H.sub.28ClN.sub.9O.sub.7S.sub.2.mult- idot.3.1H.sub.2O.
[1003] Calculated: C, 40.60; H, 4.86; N, 17.76; Cl, 4.993; S, 9.03
(%). Found: C, 40.63; H, 4.81; N, 17.74; Cl, 4.891; S, 8.88
(%).
EXAMPLE 96
[1004] 145
[1005] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.0 Hz),
2.21-2.32 (2H, m), 3.20-3.25 (4H, m), 3.37 and 3.61 (2H, ABq,
J=18.5 Hz), 3.83 (2H, t, J=5.0 Hz), 4.29 (2H, t, J=7.1 Hz), 4.99
(1H, q, J=7.0 Hz), 5.29 (1H, d, J=4.5 Hz), 5.50 and 5.68 (2H, ABq,
J=15.2 Hz), 5.92 (1H, d, J=4.5 Hz), 7.34 (2H, tike), 7.66 (1H, d,
J=7.8 Hz), 8.13 (1H, d, J=6.6 Hz).
[1006] IR (KBr) cm.sup.-1: 3368, 1773, 1627, 1556, 1455, 1395,
1349, 1321, 1287, 1090, 1158, 1093, 1065, 1034.
[1007] MS(ESI): 723.sup.+(M+H).sup.+.
[1008] Elementary Analysis as
C.sub.27H.sub.31ClN.sub.10O.sub.8S.sub.2.mul-
tidot.2.8H.sub.2O.
[1009] Calculated: C, 41.92; H, 4.77; N, 18.11; Cl, 4.58; S, 8.29
(%). Found: C, 41.93; H, 4.73; N, 18.06; Cl, 4.46; S, 8.17 (%).
EXAMPLE 97
[1010] 146
[1011] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.43 (3H, d, J=6.9 Hz),
1.55 (3H, d, J=7.2 Hz), 2.78 (3H, s), 3.40 and 3.61 (2H, ABq,
J=18.6 Hz), 3.83-3.95 (1H, m), 4.39-4.60 (2H, m), 5.00 (1H, q,
J=6.9 Hz), 5.29 (1H, d, J=4.8 Hz), 5.51 and 5.72 (2H, ABq, J=15.2
Hz), 5.92 (1H, d, J=4.8 Hz), 7.34 (1H, dd, J=6.9, 8.1 Hz), 8.02
(1H, d, J=8.1 Hz), 8.18 (1H, d, J=6.9 Hz). IR (KBr) cm.sup.-1:
3372, 3185, 1772, 1667, 1600, 1563, 1493, 1394, 1353, 1317, 1287,
1225, 1166, 1090, 1033.
[1012] MS(ESI): 693(M+H).sup.+.
[1013] Elementary Analysis as
C.sub.26H.sub.29ClN.sub.10O.sub.7S.sub.2.mul-
tidot.2.7H.sub.2O.
[1014] Calculated: C, 42.10; H, 4.67; N, 18.88; Cl, 4.78; S, 8.65
(%). Found: C, 42.15; H, 4.72; N, 18.88; Cl, 4.61; S, 8.40 (%).
EXAMPLE 98
[1015] 147
[1016] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.44 (3H, d, J=6.3 Hz),
1.55 (3H, d, J=7.2 Hz), 3.38 and 3.59 (2H, ABq, J=18.6 Hz), 3.96
(1H, m), 4.41 (2H, d, J=5.7 Hz), 4.98 (1H, q, J=7.2), 5.27 (1H, d,
J=4.7 Hz), 5.47 and 5.71 (2H, ABq, J=14.6 Hz), 5.91 (1H, d, J=4.7
Hz), 7.35 (1H, m), 8.00 (1H, d, J=8.1 Hz), 8.17 (1H, d, J=6.9
Hz).
[1017] IR (KBr) cm.sup.-1: 3358, 3184, 1771, 1651, 1563, 1494,
1396, 1365, 1317, 1288, 1225, 1166, 1090, 1034.
[1018] MS(ESI): 679.sup.+(M+H.sup.+).
[1019] Elementary Analysis as
C.sub.25H.sub.27ClN.sub.10O.sub.7S.sub.2.mul-
tidot.2.9H.sub.2O.
[1020] Calculated: C, 41.06; H, 4.52; N, 19.15; Cl, 4.85; S, 8.77
(%). Found: C, 41.06; H, 4.46; N, 19.14; Cl, 4.75; S, 8.62 (%).
EXAMPLE 99
[1021] 148
[1022] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.36 (3H, d, J=7.0 Hz),
2.96 and 3.47 (2H, ABq, J=17.7 Hz), 3.26 (2H, brs), 4.21 (2H, brs),
4.53 (1H, q, J=7.0 Hz), 5.03 (1H, q, J=5.1 Hz), 5.26 and 5.38 (2H,
ABq, J=13.5 Hz), 5.72 (1H, dd, J=5.1, 9.0 Hz), 6.67 (2H, brs), 6.83
(1H, brs), 7.30 (1H, t-like), 7.41 (2H, brs), 7.93 (1H d, J=7.5
Hz), 8.51 (1H, brs), 8.81 (1H, d, J=6.6 Hz), 9.80 (1H, brs).
[1023] IR (KBr) cm.sup.-1: 3382, 3194, 1766, 1667, 1651, 1609,
1568, 1496, 1444, 1389, 1345, 1304, 1214, 1156, 1076, 1036.
[1024] MS(ESI): 744.sup.+(M+H).sup.+.
[1025] Elementary Analysis as
C.sub.24H.sub.26ClN.sub.11O.sub.9S.sub.3.mul-
tidot.3.0H.sub.2O.
[1026] Calculated: C, 36.11; H, 4.04; N, 19.30; Cl, 4.44; S, 12.05
(%). Found: C, 35.88; H, 3.93; N, 19.18; Cl, 4.54; S, 12.17
(%).
EXAMPLE 100
[1027] 149
[1028] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.54 (3H, d, J=6.9 Hz),
3.36 and 3.61 (2H, ABq, J=18.6 Hz), 3.97 (2H, t, J=4.8 Hz), 4.30
(2H, t, J=4.8 Hz), 5.29 (1H, d, J=4.8 Hz), 5.54 and 5.68 (2H, ABq,
J=15.3 Hz), 5.92 (1H, d, J=4.8 Hz), 7.34 (1H, t-like), 7.97 (1H d,
J=7.8 Hz), 8.14 (1H, d, J=6.9 Hz).
[1029] IR (KBr) cm.sup.-1: 3357, 3190, 1758, 1669, 1648, 1618,
1574, 1540, 1492, 1460, 1443, 1412, 1395, 1362, 1342, 1297, 1265,
1236, 1210, 1168, 1074, 1028.
[1030] MS(ESI): 666.sup.+(M+H).sup.+.
[1031] Elementary Analysis as
C.sub.24H.sub.24ClN.sub.9O.sub.8S.sub.2.mult- idot.1.7H.sub.2O.
[1032] Calculated: C, 41.37; H, 3.96; N, 18.09; Cl, 5.09; S, 9.20
(%). Found: C, 41.53; H, 3.80; N, 18.19; Cl, 4.64; S, 8.79 (%).
EXAMPLE 101
[1033] 150
[1034] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.1 Hz),
2.20 (2H, m), 3.37 (1H, d, J=18.3 Hz), 3.50-3.64 (2H, m), 3.77 (1H,
dd, J=6.0, 12.3 Hz), 3.94 (1H, dd, J=4.2, 12.3 Hz), 4.30 (2H, t,
J=7.8 Hz), 5.30 (1H, d, J=4.8 Hz), 5.51 and 5.68 (2H, ABq, J=15.2
Hz), 5.92 (1H, d, J=4.8 Hz), 7.35 (1H, t-like), 8.00 (1H d, J=7.8
Hz), 8.14 (1H, d, J=6.6 Hz).
[1035] IR (KBr) cm.sup.-1: 3613, 3415, 3339, 3191, 1763, 1703,
1670, 1620, 1570, 1532, 1497, 1443, 1392, 1357, 1345, 1309, 1289,
1265, 1214, 1168, 1154, 1084, 1061, 1029.
[1036] MS(ESI): 709.sup.+(M+H).sup.+.
[1037] Elementary Analysis as
C.sub.26H.sub.29ClN.sub.10O8.sub.7S.sub.2.mu-
ltidot.2.3H.sub.2O.
[1038] Calculated: C, 41.60; H, 4.51; N, 18.66; Cl, 4.72; S, 8.54
(%). Found: C, 41.66; H, 4.19; N, 18.68; Cl, 4.65; S, 7.87 (%).
EXAMPLE 102
[1039] 151
[1040] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.2 Hz),
2.13 (3H, s), 2.17-2.35 (2H, m), 3.38 and 3.61 (2H, ABq, J=18.6
Hz), 3.74-3.81 (1H, m), 4.24-4.44 (4H, m), 4.99 (1H, q, J=7.2 Hz),
5.29 (1H, d, J=4.8 Hz), 5.51 and 5.69 (2H, ABq, J=15.0 Hz), 5.92
(1H, d, J=4.8 Hz), 7.36 (1H, dd, J=6.6, 8.1 Hz), 8.00 (1H d, J=8.1
Hz), 8.15 (1H, d, J=6.6 Hz).
[1041] IR (KBr) cm.sup.-1: 3371, 3182, 1773, 1651, 1604, 1562,
1495, 1393, 1367, 1317, 1285, 1229, 1166, 1035.
[1042] MS(ESI): 751.sup.+(M+H).sup.+.
[1043] Elementary Analysis as
C.sub.28H.sub.31ClN.sub.10O.sub.9S.sub.2.mul-
tidot.3.4H.sub.2O.
[1044] Calculated: C, 41.39; H, 4.69; N, 17.24; Cl, 4.36; S, 7.89
(%). Found: C, 41.23; H, 4.31; N, 17.10; Cl, 4.01; S, 7.97 (%).
EXAMPLE 103
[1045] 152
[1046] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.5 Hz),
3.37-3.57 (4H, m), 3.67 (3H, s), 3.93-4.02 (2H, m), 5.00 (1H, sept,
J=7.5 Hz), 5.25 (1H, d, J=5.1 Hz), 5.46 and 5.93 (2H, ABq, J=15.0
Hz), 5.91 (1H, d, J=5.1), 7.53 (1H, t, J=6.6 Hz), 7.94 (1H, d,
J=6.6 Hz), 8.15 (1H, d, J=6.6 Hz).
[1047] IR (KBr) cm.sup.-1: 3309, 1773, 1636, 1598, 1539, 1501,
1452, 1390, 1357, 1317, 1285, 1142, 1093, 1072, 1034, 988.
[1048] MS(ESI): 693.sup.+(M+H).sup.+.
[1049] Elementary Analysis as
C.sub.26H.sub.29ClN.sub.10O.sub.7S.sub.2.mul-
tidot.3.9H.sub.2O.
[1050] Calculated: C, 41.89; H, 4.71; N, 18.79; Cl, 4.76; S, 8.60
(%). Found: C, 42.03; H, 4.98; N, 18.70; Cl, 4.60; S, 8.57 (%).
EXAMPLE 104
[1051] 153
[1052] .sup.1H-NMR (D.sub.2O DCl) .delta.:1.54 (3H, d, J=7.2 Hz),
2.17-2.30 (2H, m), 2.72 (3H, s), 3.11-3.20 (2H, m), 3.36 and 3.66
(2H, ABq, J=18.3 Hz), 3.94 (3H, s), 4.18-4.27 (2H, m), 4.97 (1H,
sept, J=7.2 Hz), 5.30 (1H, d, J=5.1 Hz), 5.60 and 5.73 (2H, ABq,
J=15.2 Hz), 5.92 (1H, d, J=5.1 Hz), 7.44-7.50 (H, m), 8.14 (1H, d,
J=8.1 Hz), 8.28 (1H, d, J=6.3 Hz).
[1053] IR (KBr) cm.sup.-1: 3398, 1775, 1599, 1490, 1393, 1315,
1223, 1162, 1095, 1063, 1035, 968.
[1054] MS(ESI): 723.sup.+(M+H).sup.+.
[1055] Elementary Analysis as
C.sub.27H.sub.31ClN.sub.10O.sub.8S.sub.2.mul-
tidot.3.7H.sub.2O.
[1056] Calculated: C, 41.06; H, 4.90; N, 17.73; Cl, 4.49; S, 8.12
(%). Found: C, 41.11; H, 4.67; N, 17.59; Cl, 4.59; S, 8.01 (%).
EXAMPLE 105
[1057] 154
[1058] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.45 (3H, d, J=6.9 Hz),
2.18 (3H, s), 2.76 (3H, s), 3.15 and 3.55 (2H, ABq, J=18.0 Hz),
3.34 (2H, t, J=6.0 Hz), 3.80 (2H, t, J=6.0 Hz), 4.68 (1H, q, J=6.9
Hz), 4.89 and 5.09 (2H, ABq, J=14.7 Hz), 5.23 (1H, d, J=4.8 Hz),
5.85 (1H, d, J=4.8 Hz), 6.93 (1H, d, J=7.2 Hz), 8.08 (1H, brs),
8.22 (1H, d, J=7.2 Hz).
[1059] IR (KBr) cm.sup.-1: 3383, 1773, 1649, 1554, 1449, 1395,
1288, 1213, 1190, 1154, 1094, 1065, 1035.
[1060] MS(ESI): 653.sup.+(M+H).sup.+.
[1061] Elementary Analysis as
C.sub.25H.sub.29ClN.sub.8O.sub.7S.sub.2.mult- idot.3.0H.sub.2O.
[1062] Calculated: C, 42.46; H, 4.99; N, 1585; Cl, 5.01; S,
9.07(%). Found: C, 42.47; H, 4.77; N, 15.81; Cl, 5.86; S, 8.84
(%).
EXAMPLE 106
[1063] 155
[1064] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.45 (3H, d, J=7.2 Hz),
2.76 (3H, s), 3.16 and 3.58 (2H, ABq, J=17.4 Hz), 3.36 (2H, t,
J=6.3 Hz), 3.82 (2H, t, J=6.3 Hz), 4.64-4.72 (3H, m), 4.91 and 5.13
(2H, ABq, J=14.7 Hz), 5.24 (1H, d, J=4.8 Hz), 5.86 (1H, d, J=4.8
Hz), 7.02 (1H, d, J=7.5 Hz), 8.24 (1H, brs), 8.29(1H, d, J=7.5
Hz).
[1065] IR (KBr) cm.sup.-1: 3366, 1772, 1651, 1588, 1551, 1457,
1395, 1288, 1205, 1150, 1094, 1035.
[1066] MS(ESI): 669.sup.+(M+H).sup.+.
[1067] Elementary Analysis as
C.sub.25H.sub.29ClN.sub.8O.sub.8S.sub.2.mult- idot.3.3H.sub.2O.
[1068] Calculated: C, 41.21; H, 4.93; N, 15.38; Cl, 4.87; S, 8.80
(%). Found: C, 41.38; H, 4.73; N, 15.53; Cl, 4.77; S, 8.51 (%).
EXAMPLE 107
[1069] 156
[1070] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.56 (3H, d, J=6.9 Hz),
2.18-2.31 (2H, m), 2.71 (3H, s), 3.11-3.19 (2H, m), 3.43 and 3.51
(2H, ABq, J=17.9 Hz), 4.25-4.35 (2H, m), 4.43 (2H, s), 4.18 (1H,
sept, J=6.9 Hz), 5.20 (1H, d, J=4.8 Hz), 5.35 and 5.91 (2H, ABq,
J=15.2 Hz), 5.90 (1H, d, J=4.8 Hz), 7.34-7.40 (1H, m), 8.02 (1H, d,
J=7.5 Hz), 8.18 (1H, d, J=6.6 Hz).
[1071] IR (KBr) cm.sup.-1: 3409, 1774, 1635, 1593, 1540, 1496,
1390, 1314, 1228, 1188, 1165, 1112, 1073, 1034, 984, 759.
[1072] MS(FAB): 751.sup.+(M+H).sup.+.
[1073] Elementary Analysis as
C.sub.28H.sub.31ClN.sub.10O.sub.9S.sub.2.mul-
tidot.2.3H.sub.2O.
[1074] Calculated: C, 42.43; H, 4.53; N, 17.67; Cl, 4.47; S, 8.09
(%). Found: C, 42.50; H, 4.16; N, 17.66; Cl, 4.40; S, 7.88 (%).
EXAMPLE 108
[1075] 157
[1076] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.43 (3H, d, J=6.9 Hz),
1.55 (3H, d, J=7.1 Hz), 2.17 (2H, m), 3.35 and 3.59 (2H, ABq,
J=18.6 Hz), 3.51 (1H, m), 4.28 (2H, t-ike), 4.97 (1H, q, J=7.1),
5.27 (1H, d, J=4.8 Hz), 5.45 and 5.67 (2H, ABq, J=15.0 Hz), 5.91
(1H, d, J=4.8 Hz), 7.3 (1H, t-like), 7.97 (1H, d, J=7.8 Hz), 8.13
(1H, d, J=6.9 Hz).
[1077] IR (KBr) cm.sup.-1: 3408, 1773, 1650, 1601, 1565, 1495,
1395, 1363, 1317, 1287, 1224, 1165, 1090, 1034.
[1078] MS(ESI): 693.sup.+(M+H.sup.+).
[1079] Elementary Analysis as
C.sub.26H.sub.29ClN.sub.10O.sub.7S.sub.2.mul-
tidot.3.7H.sub.2O.
[1080] Calculated: C, 41.10; H, 4.83; N, 18.43; Cl, 4.67; S, 8.44
(%). Found: C, 41.15; H, 4.69; N, 18.33; Cl, 4.65; S, 8.17 (%).
EXAMPLE 109
[1081] 158
[1082] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 0.97 (3H, t, J=7.4 Hz),
1.48 (2H, m), 1.55 (3H, d, J=7.2 Hz), 1.91 (2H, q, J=7.5 Hz), 2.23
(2H, m), 3.15 (2H, t, J=7.5 Hz), 3.42 and 3.64 (2H, ABq, J=18.3
Hz), 3.61 (1H, m), 4.58 (2H, t like), 4.99 (1H, q, J=7.2), 5.28
(1H, d, J=4.8 Hz), 5.73 and 6.02 (2H, ABq, J=15.0 Hz), 5.73 (1H, d,
J=4.8 Hz), 7.79 (1H, t like), 8.67 (1H, d, J=8.1 Hz), 8.72 (1H, d,
J=6.3 Hz).
[1083] IR (KBr) cm.sup.-1: 3399, 2959, 2872, 1776, 1601, 1540,
1465, 1396, 1349, 1318, 1224, 1161, 1093, 1064, 1033.
[1084] MS(ESI): 734.sup.+(M+H.sup.+).
[1085] Elementary Analysis as
C.sub.30H.sub.36ClN.sub.9O.sub.7S.sub.2.mult- idot.3.8H.sub.2O.
[1086] Calculated: C, 44.89; H, 5.47; N, 15.70; Cl, 4.42; S, 7.99
(%). Found: C, 44.79; H, 5.22; N, 15.82; Cl, 4.32; S, 7.89 (%).
EXAMPLE 110
[1087] 159
[1088] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.53 (3H, d, J=7.2 Hz),
2.85 (3H, s), 3.39 and 3.80 (2H, ABq, J=18.6 Hz), 3.88 (2H, t,
J=5.7 Hz), 4.97 (1H, q, J=7.2 Hz), 5.31 (2H, t, J=5.7 Hz), 5.37
(1H, d, J=4.7 Hz), 5.54-6.00 (2H, m), 5.95 (1H, d, J=4.7 Hz), 8.50
(1H, d, J=7.2 Hz), 8.96 (1H, d, J=7.2 Hz), 10.16(1H, s).
[1089] IR (KBr) cm.sup.-1: 3407, 1774, 1609, 1539, 1483, 1447,
1394, 1359, 1287, 1190, 1155, 1104, 1066, 1034.
[1090] MS(ESI): 665.sup.+(M+H.sup.+).
[1091] Elementary Analysis as
C.sub.24H.sub.25ClN.sub.10O.sub.7S.sub.2.mul-
tidot.3.2H.sub.2O.
[1092] Calculated: C, 39.88; H, 4.38; N, 19.38; Cl, 4.91; S, 8.87
(%). Found: C, 39.93; H, 4.02; N, 19.34; Cl, 4.76; S, 8.64 (%).
EXAMPLE 111
[1093] 160
[1094] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.2 Hz),
2.68 (2H, m), 3.36 and 3.60 (2H, ABq, J=18.6 Hz), 3.57 and 3.97
(4H, m), 4.99 (1H, m), 5.29 (1H, d, J=5.0 Hz), 5.50 and 5.69 (2H,
ABq, J=15.2 Hz), 5.92 (1H, d, J=5.0 Hz), 7.34 (1H, t like), 8.06
(1H, d, J=7.5 Hz), 8.16 (1H, d, J=6.6 Hz).
[1095] IR (KBr) cm.sup.-1: 3410, 1771, 1606, 1556, 1491, 1440,
1396, 1363, 1319, 1224, 1167, 1092, 1034.
[1096] MS(FAB): 691.sup.+(M+H.sup.+).
[1097] Elementary Analysis as
C.sub.26H.sub.27ClN.sub.10O.sub.7S.sub.2.mul-
tidot.4.6H.sub.2O.
[1098] Calculated: C, 40.35; H, 4.71; N, 18.10; Cl, 4.58; S, 8.29
(%). Found: C, 40.39; H, 4.17; N, 17.79; Cl, 4.49; S, 8.47 (%).
EXAMPLE 112
[1099] 161
[1100] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.5 Hz),
3.38 and 3.61 (2H, ABq, J=18.6 Hz), 4.59-4.68 (2H, m), 4.92-5.03
(2H, m), 5.29 (1H, d, J=4.8 Hz), 5.51 (1H, d, J=15.0 Hz), 5.67-5.78
(2H, m), 5.92 (1H, d, J=4.8 Hz), 7.40 (1H, dd, J=6.6, 8.1 Hz), 8.21
(1H, d, J=6.6 Hz), 8.29 (1H, d, J=8.1 Hz).
[1101] IR (KBr) cm.sup.-1: 3379, 1770, 1667, 1603, 1559, 1491,
1442, 1398, 1364, 1317, 1287, 1226, 1170, 1092, 1034.
[1102] MS(ESI): 677.sup.+(M+H).sup.+.
[1103] Elementary Analysis as
C.sub.252H.sub.25ClN.sub.10O.sub.7S.sub.2.mu-
ltidot.3.9H.sub.2O.
[1104] Calculated: C, 40.18; H, 4.42; N, 18.74; Cl, 4.74; S, 8.58
(%). Found: C, 40.36; H, 4.32; N, 18.37; Cl, 4.76; S, 8.39 (%).
EXAMPLE 113
[1105] 162
[1106] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=7.2 Hz),
1.83-2.37 (4H, m), 3.29-3.62 (4H, m), 4.07 (1H, m), 4.58 (2H, d,
J=7.2 Hz), 4.97 (1H, q, J=7.2 Hz), 5.27 (1H, d, J=5.0 Hz), 5.46 and
5.71 (2H, ABq, J=15.3 Hz), 5.91 (1H, d, J=5.0 Hz), 7.35 (1H,
t-like), 8.02 (1H, d, J=7.8 Hz), 8.17 (1H, d, J=6.6 Hz).
[1107] IR (KBr) cm.sup.-1: 3417, 1772, 1650, 1605, 1563, 1494,
1394, 1362, 1317, 1222, 1167, 1093, 1033.
[1108] MS(ESI): 705.sup.+(M+H.sup.+).
[1109] Elementary Analysis as
C.sub.27H.sub.29ClN.sub.10O.sub.7S.sub.2.mul-
tidot.4.1H.sub.2O.
[1110] Calculated: C, 41.63; H, 4.81; N, 17.98; Cl, 4.55; S, 8.23
(%). Found: C, 41.73; H, 4.66; N, 17.70; Cl, 4.74; S, 8.37 (%).
EXAMPLE 114
[1111] 163
[1112] .sup.1H-NMR (D.sub.2O) .delta.: 1.44 (3H, d, J=6.9 Hz), 2.75
(3H, s), 3.11 and 3.57 (2H, ABq, J=17.7 Hz), 3.32 (2H, t, J=5.9
Hz), 3.51 (2H, t, J=5.9 Hz), 4.66 (1H, q, J=6.9 Hz), 4.77 and 5.12
(2H, ABq, J=14.4 Hz), 5.24 (1H, d, J=4.8 Hz), 5.69 (1H, d, J=4.8
Hz), 6.83 (1H, d, J=6.3 Hz), 7.86-7.89 (2H, m).
[1113] IR (KBr) cm.sup.-1: 3371, 1773, 1600, 1546, 1492, 1457,
1394, 1358, 1284, 1185, 1157, 1093, 1066, 1034.
[1114] MS(FAB): 654.sup.+(M+H).sup.+.
[1115] Elementary Analysis as
C.sub.24H.sub.28ClN.sub.9O.sub.7S.sub.2.mult- idot.2.7H.sub.2O.
[1116] Calculated: C, 41.02; H, 4.73; N, 17.94; Cl, 5.04; S, 9.13
(%). Found: C, 41.14; H, 4.53; N, 17.91; Cl, 4.73; S, 8.55 (%).
EXAMPLE 115
[1117] 164
[1118] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.07-1.18 (2H, m), 1.38
(3H, d, J=7.2 Hz), 1.38-1.47 (2H, m), 2.20-2.38 (1H, m), 3.02 (1H,
d, J=17.7 Hz), 3.48 (1H, d, J=17.7 Hz), 4.55 (1H, q, J=7.2 Hz),
4.99 (1H, d, J=13.2 Hz), 5.05 (1H, d, J=4.2 Hz), 5.52 (1H, d,
J=13.2 Hz), 5.70 (1H, dd, J=4.2, 8.4 Hz), 7.37-7.57 (2H, m), 7.82
(2H, d, J=6.0 Hz), 9.19 (2H, d, J=6.0 Hz), 9.58-9.73 (1H, m).
[1119] IR (KBr) cm.sup.-1: 3409, 3053, 1778, 1674, 1637, 1538,
1518, 1475, 1453, 1389, 1353, 1215, 1185, 1158, 1100, 1034.
[1120] MS(FAB): 607.sup.+(M+H.sup.+).
[1121] Elementary Analysis as
C.sub.24H.sub.23ClN.sub.6O.sub.7S.sub.2.mult- idot.1.9H.sub.2O.
[1122] Calculated: C, 44.95; H, 4.21; N, 13.10; Cl, 5.53; S, 10.00
(%). Found: C, 44.93; H, 4.35; N, 13.09; Cl, 5.44; S, 10.08
(%).
EXAMPLE 116
[1123] 165
[1124] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=6.9 Hz),
3.11 (1H, d, J=17.7 Hz), 3.53 (1H, d, J=17.7 Hz), 4.54 (1H, q,
J=6.9 Hz), 5.07 (1H, d, J=4.8 Hz), 5.21 (1H, d, J=13.8 Hz), 5.72
(1H, dd, J=4.8, 8.4 Hz), 5.77 (1H, d, J=13.8 Hz), 7.41 (2H, s),
8.73 (2H, d, J=6.9 Hz), 9.51-9.82 (3H, m).
[1125] IR (KBr) cm.sup.-1: 3413, 1777, 1671, 1615, 1538, 1510,
1457, 1391, 1346, 1237, 1189, 1152, 1103, 1083, 1035.
[1126] MS(FAB): 635.sup.+(M+H.sup.+).
[1127] Elementary Analysis as
C.sub.23H.sub.19ClN.sub.8O.sub.8S.sub.2.mult- idot.3.1H.sub.2O.
[1128] Calculated: C, 39.98; H, 3.68; N, 16.22; Cl, 5.13; S, 9.28
(%). Found: C, 39.83; H, 3.62; N, 16.25; Cl, 5.25; S, 9.78 (%).
EXAMPLE 117
[1129] 166
[1130] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.37 (3H, d, J=6.9 Hz),
3.12 (1H, d, J=18.0 Hz), 3.50 (1H, d, J=18.0 Hz), 4.55 (1H, q,
J=6.9 Hz), 5.06 (1H, d, J=5.1 Hz), 5.19 (1H, d, J=13.2 Hz),
5.68-5.79 (2H, m), 7.41 (2H, s), 8.16 (1H, s), 8.46 (2H, d, J=6.6
Hz), 9.49-9.75 (3H, m).
[1131] IR (KBr) cm.sup.-1: 3287, 3196, 3055, 2988, 1779, 1673,
1618, 1538, 1457, 1345, 1242, 1188, 1119, 1065, 1035.
[1132] MS(FAB): 653.sup.+(M+H.sup.+).
[1133] Elementary Analysis as
C.sub.23H.sub.21ClN.sub.8O.sub.9S.sub.2.mult- idot.2.1H.sub.2O.
[1134] Calculated: C, 39.98; H, 3.68; N, 16.22; Cl, 5.13; S, 9.28
(%). Found: C, 39.97; H, 3.75; N, 16.57; Cl, 4.72; S, 8.79 (%).
EXAMPLE 118
[1135] 167
[1136] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.38 (3H, d, J=6.9 Hz),
3.08 (1H, d, J=17.7 Hz), 3.50 (1H, d, J=17.7 Hz), 3.99 (3H, s),
4.55 (1H, q, J=6.9 Hz), 5.06 (1H, d, J=4.5 Hz), 5.08 (1H, d, J=12.9
Hz), 5.62 (1H, d, J=12.9 Hz), 5.71 (1H, dd, J=4.5, 8.1 Hz), 7.41
(2H, s), 8.08 (1H, dd, J=5.7, 8.7 Hz), 8.22 (1H, d, J=8.7 Hz), 9.11
(1H, d, J=5.7 Hz), 9.41 (1H, s), 9.54-9.66 (1H, m).
[1137] IR (KBr) cm.sup.-1: 3410, 2942, 1778, 1674, 1618, 1539,
1509, 1444, 1389, 1340, 1290, 1235, 1188, 1148, 1099, 1041,
1009.
[1138] MS(FAB): 597.sup.+(M+H.sup.+).
[1139] Elementary Analysis as
C.sub.22H.sub.21ClN.sub.6O.sub.8S.sub.2.mult- idot.2.7H.sub.2O.
[1140] Calculated: C, 40.92; H, 4.12; N, 13.02; Cl, 5.49; S, 9.93
(%). Found: C, 40.94; H, 4.01; N, 13.12; Cl, 5.36; S, 9.91 (%).
EXAMPLE 119
[1141] 168
[1142] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39 (3H, d, J=7.2 Hz),
1.59 (3H, d, J=7.2 Hz), 3.09 (1H, d, J=17.4 Hz), 4.54 (1H, q, J=7.2
Hz), 5.00 (1H, d, J=5.4 Hz), 5.30 (1H, d, J=13.8 Hz), 5.42 (1H, d,
J=13.8 Hz), 5.55-5.67 (1H, m), 5.72 (1H, dd, J=5.4, 8.4 Hz), 7.41
(2H, s), 7.79 (1H, d, J=4.2 Hz), 8.02-8.09 (2H, m), 8.30-8.39 (1H,
m), 9.75 (1H, s).
[1143] IR (KBr) cm.sup.-1: 3410, 2353, 1775, 1669, 1612, 1537,
1447, 1382, 1319, 1289, 1237, 1185, 1152, 1098, 1068, 1034.
[1144] MS(FAB): 683.sup.+(M+H.sup.+).
[1145] Elementary Analysis as
C.sub.24H.sub.23ClN.sub.8O.sub.8S.sub.3.mult- idot.4.0H.sub.2O.
[1146] Calculated: C, 38.17; H, 4.14; N, 14.84; Cl, 4.69; S, 12.74
(%). Found: C, 38.05; H, 4.10; N, 14.78; Cl, 4.97; S, 12.98
(%).
EXAMPLE 120
[1147] 169
[1148] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.38 (3H, d, J=6.6 Hz),
1.96-2.10 (2H, m), 2.79-2.90 (2H, m), 3.03 (1H, d, J=17.7 Hz), 3.47
(1H, d, J=17.7 Hz), 4.45-4.54 (2H, m), 4.54 (1H, q, J=6.6 Hz), 4.86
(1H, d, J=13.5 Hz), 5.04 (1H, d, J=4.8 Hz), 5.43 (1H, d, J=13.5
Hz), 5.70 (1H, dd, J=4.8, 8.4 Hz), 7.38-7.48 (3H, m), 9.04 (1H, s),
9.08 (1H, d, J=6.9 Hz), 9.64-9.82 (1H, m).
[1149] IR (KBr) cm.sup.-1: 3412, 3057, 1779, 1674, 1641, 1538,
1516, 1489, 1468, 1444, 1351, 1287, 1220, 1168, 1135, 1034,
1008.
[1150] MS(FAB): 623.sup.+(M+H.sup.+).
[1151] Elementary Analysis as
C.sub.24H.sub.23ClN.sub.6O.sub.8S.sub.2.mult- idot.2.0H.sub.2O.
[1152] Calculated: C, 43.74; H, 4.13; N, 12.75; Cl, 5.38; S, 9.73
(%). Found: C, 43.71; H, 3.94; N, 12.94; Cl, 5.13; S, 9.49 (%).
EXAMPLE 121
[1153] 170
[1154] .sup.1H-NMR (D.sub.2O) .delta.: 1.45 (3H, d, J=7.2), 2.09
(2H, m), 2.71 (3H, s), 2.97 (2H, t, J=8.1 Hz), 3.10 (2H, t, J=8.1
Hz), 3.16 (1H, d, J=18.0 Hz), 3.65 (1H, d, J=18.0 Hz), 4.66 (1H, q,
J=7.2 Hz), 5.25 (1H, d, J=14.1 Hz), 5.28 (1H, d, J=5.1 Hz), 5.56
(1H, d, J=14.1 Hz), 5.88 (1H, d, J=5.1 Hz), 8.01 (1H, dd, J=6.6,
7.5 Hz), 8.45 (1H, d, J=7.5 Hz), 8.82 (1H, d, J=6.6 Hz), 8.93 (1H,
brs).
[1155] IR (KBr) cm.sup.-1: 3398, 2822, 1776, 1674, 1605, 1539,
1507, 1469, 1393, 1351, 1286, 1238, 1191, 1149, 1094, 1066,
1033.
[1156] MS (ESI): 638 (M+H).sup.+, 660 (M+Na).sup.+.
[1157] Elementary Analysis as
C.sub.25H.sub.28ClN.sub.7O.sub.7S.sub.2.mult- idot.4.0H.sub.2O.
[1158] Calculated: C, 42.28; H, 5.11; N, 13.81; Cl, 4.99; S, 9.03
(%). Found: C, 42.27; H, 5.09; N, 13.80; Cl, 5.00; S, 9.08 (%).
EXAMPLE 122
[1159] 171
[1160] .sup.1H-NMR (D.sub.2O) .delta.: 1.36 (3H, d, J=6.9), 2.04
(2H, m), 2.64 (3H, s), 2.95 (2H, t, J=7.8 Hz), 3.03 (2H, t, J=7.8
Hz), 3.11 (1H, d, J=17.7 Hz), 3.55 (1H, d, J=17.7 Hz), 4.58 (1H, q,
J=6.9 Hz), 5.17 (1H, d, J=14.7 Hz), 5.19 (1H, d, J=4.8 Hz), 5.45
(1H, d, J=14.7 Hz), 5.81 (1H, d, J=4.8 Hz), 7.86 (2H, d, J=6.9 Hz),
8.76 (2H, d, J=6.9 Hz).
[1161] IR (KBr) cm.sup.-1: 3397, 2821, 1776, 1606, 1538, 1467,
1394, 1350, 1287, 1231, 1187, 1152, 1094, 1066, 1033.
[1162] MS (ESI): 638 (M+H).sup.+, 660 (M+Na).sup.+.
[1163] Elementary Analysis as
C.sub.25H.sub.28ClN.sub.7O.sub.7S.sub.2.mult- idot.3.8H.sub.2O.
[1164] Calculated: C, 42.50; H, 5.08; N, 13.88; Cl, 5.02; S, 9.08
(%). Found: C, 42.34; H, 5.10; N, 13.97; Cl, 5.07; S, 9.29 (%).
EXAMPLE 123
[1165] 172
[1166] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.41 (3H, d, J=6.9 Hz),
2.48 (3H, s), 2.81 (1H, d, J=17.4 Hz), 2.94-3.06 (2H, m), 3.30-3.40
(2H, m), 3.50 (1H, d, J=17.4 Hz), 4.47 (1H, q, J=6.9 Hz), 4.87 (1H,
d, J=13.2 Hz), 5.12 (1H, d, J=5.4 Hz), 5.41 (1H, d, J=13.2 Hz),
5.82 (1H, dd, J=5.4, 9.0 Hz), 7.35 (2H, s), 7.58-7.74 (3H, m),
8.23-8.32 (1H, m), 9.11 (1H, s), 11.10-11.23 (1H, m).
[1167] IR (KBr) cm.sup.-1: 3362, 3086, 1774, 1593, 1539, 1511,
1458, 1394, 1353, 1288, 1184, 1154, 1095, 1065, 1033.
[1168] MS(ESI): 639.sup.+(M+H.sup.+).
[1169] Elementary Analysis as
C.sub.24H.sub.27ClN.sub.8O.sub.7S.sub.2.mult- idot.3.0H.sub.2O.
[1170] Calculated: C, 41.59; H, 4.80; N, 16.17; Cl, 5.11; S, 9.25
(%). Found: C, 41.54; H, 4.67; N, 16.18; Cl, 5.17; S, 9.45 (%).
EXAMPLE 124
[1171] 173
[1172] .sup.1H-NMR (D.sub.2O) .delta.: 1.45 (3H, d, J=6.9 Hz), 2.76
(3H, s), 3.17 (1H, d, J=18.0 Hz), 3.33 (2H, t, J=6.0 Hz), 3.58 (1H,
d, J=18.0 Hz), 3.75 (2H, t, J=6.0 Hz), 4.66 (1H, q, J=6.9 Hz), 4.89
(1H, d, J=14.7 Hz), 5.09 (1H, d, J=14.7 Hz), 5.24 (1H, d, J=4.8
Hz), 5.86 (1H, d, J=4.8 Hz), 6.94 (2H, d, J=6.3 Hz), 8.04-8.35 (2H,
m).
[1173] IR (KBr) cm.sup.-1: 3398, 3066, 1773, 1650, 1601, 1556,
1450, 1394, 1357, 1288, 1218, 1168, 1094, 1065, 1035.
[1174] MS(FAB): 639.sup.+(M+H.sup.+).
[1175] Elementary Analysis as
C.sub.24H.sub.27ClN.sub.8O.sub.7S.sub.2.mult- idot.3.4H.sub.2O.
[1176] Calculated: C, 41.16; H, 4.86; N, 16.00; Cl, 5.06; S, 9.16
(%). Found: C, 41.14; H, 4.69; N, 16.00; Cl, 4.97; S, 9.36 (%).
[1177] Quaternary Salt Ester: 174
[1178] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.15-1.40 (9H, m),
1.43-1.50 (12H, m), 1.54 (9H, s), 2.75-2.86 (3H, m), 3.20-3.38 (3H,
m), 3.45 (1H, d, J=17.7 Hz), 3.76 (3H, s), 4.00-4.16 (2H, m), 4.90
(1H, q, J=6.9 Hz), 5.21 (1H, d, J=12.6 Hz), 5.21 (1H, d, J=5.1 Hz),
5.28 (1H, d, J=12.6 Hz), 5.41 (2H, s), 5.97 (1H, dd, J=5.1, 8.1
Hz), 6.83 (1H, s), 6.93 (2H, d, J=8.1 Hz), 7.20-7.44 (12H, m), 8.09
(2H, d, J=7.5 Hz), 8.73 (2H, d, J=7.5 Hz), 9.73 (1H, d, J=8.1 Hz),
12.08 (1H, s).
[1179] IR (KBr) cm.sup.-1: 3425, 2978, 2934, 1793, 1724, 1693,
1638, 1613, 1551, 1516, 1479, 1455, 1393, 1369, 1249, 1223, 1153,
1065, 1036.
[1180] MS(FAB): 1225.sup.+(M.sup.+).
EXAMPLE 125
[1181] 175
[1182] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39 (3H, d, J=6.9 Hz),
1.47 (3H, d, J=6.6 Hz), 3.15 (1H, d, J=17.4 Hz), 3.40 (3H, d,
J=17.4 Hz), 4.55 (1H, q, J=6.9 Hz), 4.99-50.6 (2H, m), 5.27 (1H, d,
J=13.8 Hz), 5.42 (1H, d, J=13.8 Hz), 5.71 (1H, dd, J=5.1, 9.0 Hz),
7.41 (2H, br s), 7.70 (1H, d, J=4.2 Hz), 8.06 (1H, m), 8.45 (1H, d,
J=4.2 Hz), 9.78 (1H, br s).
[1183] IR (KBr) cm.sup.-1: 3394, 1773, 1670, 1613, 1537, 1446,
1354, 1183, 1152, 1094, 1066, 1035.
[1184] MS (FAB): 655 (M+H).sup.+, 1309 (2M+H).sup.+.
[1185] Elementary Analysis as
C.sub.23H.sub.23ClN.sub.8O.sub.7S.sub.3.mult- idot.3.6H.sub.2O.
[1186] Calculated: C, 38.37; H, 4.23; N, 15.56; Cl, 4.92; S, 13.36
(%). Found: C, 38.61; H, 4.01; N, 15.58; Cl, 4.92; S, 13.08
(%).
EXAMPLE 126
[1187] 176
[1188] .sup.1H-NMR (D.sub.2O) .delta.: 1.38 (3H, d, J=7.2), 2.89
(1H, d, J=18.0 Hz), 3.17 (2H, t, J=7.2 Hz), 3.33 (2H, t, J=7.2 Hz),
3.70 (1H, d, J=18.0 Hz), 4.62 (1H, q, J=7.2 Hz), 5.20 (1H, d,
J=15.0 Hz), 5.29 (1H, d, J=4.8 Hz), 5.83 (1H, d, J=4.8 Hz), 6.00
(1H, d, J=15.0 Hz), 7.58 (1H, br t, J=7.5 Hz), 7.64 (1H, s), 8.50
(1H, d, J=6.0 Hz), 8.65 (1H, d, J=7.5 Hz).
[1189] IR (KBr) cm.sup.-1: 3396, 3184, 2821, 1772, 1598, 1539,
1445, 1384, 1361, 1288, 1219, 1188, 1157, 1093, 1061, 1035.
[1190] MS (FAB): 649 (M+H).sup.+, 1297 (2M+H).sup.+.
[1191] Elementary Analysis as
C.sub.25H.sub.25ClN.sub.8O.sub.7S.sub.2.mult- idot.3.8H.sub.2O.
[1192] Calculated: C, 41.85; H, 4.58; N, 15.62; Cl, 4.94; S, 8.94
(%). Found: C, 41.78; H, 4.34; N, 15.66; Cl, 4.98; S, 8.77 (%).
EXAMPLE 127
[1193] 177
[1194] .sup.1H-NMR (D.sub.2O) .delta.: 1.46 (3H, d, J=6.9), 2.76
(3H, s), 3.18 (1H, d, J=18.0 Hz), 3.23 (3H, s), 3.36 (2H, t, J=6.9
Hz), 3.58 (1H, d, J=18.0 Hz), 3.95 (2H, t, J=6.9 Hz), 4.68 (1H, q,
J=6.9 Hz), 4.91 (1H, d, J=15.0 Hz), 5.10 (1H, d, J=15.0 Hz), 5.24
(1H, d, J=4.8 Hz), 5.86 (1H, d, J=4.8 Hz), 7.01 (2H, d, J=7.5 Hz),
8.24 (2H, d, J=7.5 Hz).
[1195] IR (KBr) cm.sup.-1: 3408, 1775, 1650, 1606, 1556, 1450,
1404, 1359, 1286, 1235, 1164, 1106, 1064, 1034.
[1196] MS (FAB): 653 (M+H).sup.+, 1305 (2M+H).sup.+.
[1197] Elementary Analysis as
C.sub.25H.sub.29ClN.sub.8O.sub.7S.sub.2.mult- idot.3.7H.sub.2O.
[1198] Calculated: C, 41.72; H, 5.10; N, 15.77; Cl, 4.93; S, 8.91
(%). Found: C, 41.79; H, 4.94; N, 15.48; Cl, 4.92; S, 8.78 (%).
EXAMPLE 128
[1199] 178
[1200] .sup.1H-NMR (D.sub.2O) .delta.: 1.45 (3H, d, J=6.9), 3.17
(1H, d, J=18.0 Hz), 3.45 (4H, m), 3.58 (1H, d, J=18.0 Hz), 3.97
(4H, m), 4.66 (1H, q, J=6.9 Hz), 4.92 (1H, d, J=15.0 Hz), 5.13 (1H,
d, J=15.0 Hz), 5.24 (1H, d, J=4.8 Hz), 5.86 (1H, d, J=4.8 Hz), 7.15
(2H, d, J=7.8. Hz), 8.27 (2H, d, J=7.8 Hz).
[1201] IR (KBr) cm.sup.-1: 3398, 1771, 1649, 1603, 1544, 1450,
1385, 1362, 1283, 1239, 1175, 1151, 1093, 1065, 1035.
[1202] MS (ESI): 651 (M+H).sup.+, 673 (M+Na).sup.+.
[1203] Elementary Analysis as
C.sub.25H.sub.27ClN.sub.8O.sub.7S.sub.2.mult- idot.3.7H.sub.2O.
[1204] Calculated: C, 41.83; H, 4.83; N, 15.61; Cl, 4.94; S, 8.93
(%). Found: C, 41.79; H, 4.72; N, 15.71; Cl, 4.97; S, 8.96 (%).
EXAMPLE 129
[1205] 179
[1206] .sup.1H-NMR (D.sub.2O) .delta.: 1.52 (3H, d, J=7.2), 2.89
(3H/2, s), 3.04 (3H/2, s), 3.18 (1H, br d, J=18.0 Hz), 3.52-3.62
(5H, m), 4.84 (1H, q, J=7.2 Hz), 4.90 (1H, d, J=15.0 Hz), 5.05 (1H,
d, J=15.0 Hz), 5.25 (1H, d, J=4.8 Hz), 5.86 (1H, d, J=4.8 Hz), 6.88
(2H, m), 7.88 (1H/2, s), 7.99 (1H/2, s), 8.02-8.19 (2H,m).
[1207] IR (KBr) cm.sup.-1: 3406, 1778, 1650, 1554, 1446, 1391,
1352, 1219, 1170, 1096, 1064, 1034.
[1208] MS (ESI): 667 (M+H).sup.+.
[1209] Elementary Analysis as
C.sub.25H.sub.27ClN.sub.8O.sub.8S.sub.2.mult- idot.2.7H.sub.2O.
[1210] Calculated: C, 41.95; H, 4.56; N, 15.66; Cl, 4.95; S, 8.96
(%). Found: C, 41.93; H, 4.40; N, 15.73; Cl, 5.12; S, 8.93 (%).
EXAMPLE 130
[1211] 180
[1212] .sup.1H-NMR (D.sub.2O) .delta.: 1.44 (3H, d, J=6.6 Hz),
1.69-1.90 (2H, m), 2.20-2.34 (2H, m), 3.09-3.25 (3H, m), 3.44-3.62
(3H, m), 3.84-4.00 (1H, m), 4.65 (1H, q, J=6.6 Hz), 4.86 (1H, d,
J=14.7 Hz), 5.06 (1H, d, J=14.7 Hz), 5.23 (1H, d, J=5.1 Hz), 5.86
(1H, d, J=5.1 Hz), 6.80-7.00 (2H, m), 7.96-8.28 (2H, m).
[1213] IR (KBr) cm.sup.-1: 3395, 2527, 1773, 1650, 1594, 1553,
1453, 1387, 1287, 1217, 1166, 1097, 1066, 1034.
[1214] MS(FAB): 665.sup.+(M+H.sup.+).
[1215] Elementary Analysis as
C.sub.26H.sub.29ClN.sub.8O.sub.7S.sub.2.mult- idot.6.2H.sub.2O.
[1216] Calculated: C, 40.20; H, 5.37; N, 14.42; Cl, 4.56; S, 8.26
(%). Found: C, 40.13; H, 5.07; N, 14.45; Cl, 4.81; S, 8.37 (%).
EXAMPLE 131
[1217] 181
[1218] .sup.1H-NMR (D.sub.2O) .delta.: 1.56 (3H, d, J=7.2 Hz),
2.13-2.25 (1H, m), 2.45-2.58 (1H, m), 3.28 and 3.64 (2H, ABq,
J=18.3 Hz), 3.36-3.77 (4H, m), 4.53-4.60 (1H, m,), 4.96 (1H, q,
J=6.9 Hz), 4.99 and 5.25 (2H, ABq, J=14.7 Hz), 5.30 (1H, d, J=4.8
Hz), 5.90 (1H, d, J=4.8 Hz), 6.82 (2H, d, J=7.2 Hz), 8.18 (1H,
m).
[1219] IR (KBr) cm.sup.-1: 1773, 1650, 1597, 1551, 1446, 1391,
1286, 1217, 1167.
[1220] MS (ESI): 651 (M+H).sup.+, 673 (M+Na).sup.+.
[1221] Elementary Analysis as
C.sub.25H.sub.27ClN.sub.8O.sub.7S.sub.2.mult- idot.2.7H.sub.2O.
[1222] Calculated: C, 42.91; H, 4.67; N, 16.01; Cl, 5.07; S, 9.17
(%). Found: C, 42.98; H, 4.64; N, 15.99; Cl, 4.97; S, 9.29 (%).
EXAMPLE 132
[1223] 182
[1224] .sup.1H-NMR (D.sub.2O) .delta.: 1.56 (3H, d, J=7.2 Hz),
2.16-2.24 (1H, m), 2.46-2.58 (1H, m), 3.29 and 3.64 (2H, ABq,
J=18.2 Hz), 3.37-3.78 (4H, m), 4.53-4.60 (1H, m,), 4.96 (1H, q,
J=7.2 Hz), 5.00 and 5.26 (2H, ABq, J=14.7 Hz), 5.30 (1H, d, J=4.8
Hz), 5.90 (1H, d, J=4.8 Hz), 6.96 (2H, d, J=7.5 Hz), 8.20 (1H,
m).
[1225] IR (KBr) cm.sup.-1: 1774, 1650, 1595, 1551, 1446, 1391,
1286, 1218, 1167.
[1226] MS (ESI): 651 (M+H).sup.+, 673 (M+Na).sup.+.
[1227] Elementary Analysis as
C.sub.25H.sub.27ClN.sub.8O.sub.7S.sub.2.mult- idot.2.2H.sub.2O.
[1228] Calculated: C, 43.47; H, 4.58; N, 16.22; Cl, 5.13; S, 9.28
(%). Found: C, 43.40; H, 4.60; N, 16.25; Cl, 5.07; S, 9.28 (%).
[1229] Quaternary Salt Ester: 183
[1230] .sup.1H-NMR (DMSO) .delta.: 1.41 (9H, s), 1.46-1.48 (12H,
m), 1.78-1.96 (1H, m), 2.10-2.30 (1H, m), 3.11-3.25 (1H, m), 3.37,
3.49 (ABq, J=18.9 Hz), 3.54-3.76 (2H, m), 3.76 (3H, s), 4.19-4.36
(1H, m), 4.90 (1H, q, J=6.9 Hz), 5.04-5.15 (2H,m), 5.20(1H,d,J=5.1
Hz), 5.21, 5.26(2H,Abq,J=11.7 Hz), 5.96(1H,dd,J=4.8 Hz,J=8.1 Hz),
6.84(1H,s)6.866.97(4H,m), 7.07(1H,d,J=7.8 Hz), 7.19, 7.48(10H,m),
8.07, 8.09(1H,m), 8.27(1H,d,J=7.5 Hz), 8.92, 8.94(1H,m),
9.74(1H,J=8.4 Hz), 12.11(1H,s).
EXAMPLE 133
[1231] 184
[1232] .sup.1H-NMR (D.sub.2O) .delta.: 1.45 (3H, d, J=6.9), 2.04
(3H, m), 2.72 (3H, s), 3.12 (2H, t, J=7.8 Hz), 3.16 (1H, d, J=18.0
Hz), 3.44 (2H, t, J=6.9 Hz), 3.56 (1H, d, J=18.0 Hz), 4.66 (1H, q,
J=6.9 Hz), 4.86 (1H, d, J=14.4 Hz), 5.05 (1H, d, J=14.4 Hz), 5.23
(1H, d, J=4.8 Hz), 5.86 (1H, d, J=4.8 Hz), 6.85 (2H, d, J=7.5 Hz),
8.02-8.18 (2H, m).
[1233] IR (KBr) cm.sup.-1: 3397, 1773, 1651, 1598, 1556, 1462,
1395, 1360, 1288, 1216, 1168, 1093, 1065, 1034.
[1234] MS (ESI): 653 (M+H).sup.+, 675 (M+Na).sup.+.
[1235] Elementary Analysis as
C.sub.25H.sub.29ClN.sub.8O.sub.7S.sub.2.mult- idot.3.8H.sub.2O.
[1236] Calculated: C, 41.61; H, 5.11; N, 15.53; Cl, 4.91; S, 8.89
(%). Found: C, 41.47; H, 5.08; N, 15.63; Cl, 5.15; S, 8.98 (%).
EXAMPLE 134
[1237] 185
[1238] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39 (3H, d, J=6.9),
2.97 (1H, d, J=18.0 Hz), 3.34 (2H, m), 3.46 (1H, J=18.0 Hz), 3.59
(2H, t, J=5.1 Hz), 4.56 (1H, q, J=6.9 Hz), 4.65 (1H, d, J=13.5 Hz),
5.05 (1H, d, J=4.8 Hz), 5.16 (1H, d, J=13.5 Hz), 5.70 (1H, dd,
J=4.8, 8.4 Hz), 6.94 (2H, m), 7.41 (2H, br s), 8.44 (1H, d, J=6.9
Hz), 8.59 (1H, d, J=7.5 Hz), 8.85 (1H, 5.4 Hz), 9.65 (1H, br).
[1239] IR (KBr) cm.sup.-1: 3398, 1776, 1651, 1555, 1450, 1378,
1350, 1218, 1171, 1097, 1063, 1035.
[1240] MS (ESI): 626 (M+H).sup.+, 1251 (2M+H).sup.+.
[1241] Elementary Analysis as
C.sub.23H.sub.24ClN.sub.7O.sub.8S.sub.2.mult- idot.2.3H.sub.2O.
[1242] Calculated: C, 41.39; H, 4.32; N, 14.69; Cl, 5.31; S, 9.61
(%). Found: C, 41.39; H, 4.34; N, 14.78; Cl, 5.11; S, 9.37 (%).
EXAMPLE 135
[1243] 186
[1244] .sup.1H-NMR (D.sub.2O) .delta.: 1.40 (3H, d, J=6.3), 1.45
(3H, d, J=6.9 Hz), 3.17 (1H, d, J=18.0 Hz), 3.34 (1H, m), 3.55-3.61
(4H, m), 4.28-4.33 (2H, m), 4.66 (1H, q, J=6.9 Hz), 4.91 (1H, d,
J=14.7 Hz), 5.12 (1H, d, J=14.7 Hz), 5.24 (1H, d, J=4.8 Hz), 5.86
(1H, d, J=4.8 Hz), 7.16 (2H, d, J=7.2 Hz), 8.27 (2H, d, J=7.2
Hz).
[1245] IR (KBr) cm.sup.-1: 3408, 1773, 1649, 1605, 1546, 1449,
1386, 1360, 1284, 1239, 1158, 1107, 1065, 1036.
[1246] MS (ESI): 665 (M+H).sup.+, 687 (M+Na).sup.+.
[1247] Elementary Analysis as
C.sub.26H.sub.29ClN.sub.8O.sub.7S.sub.2.mult- idot.4.5H.sub.2O.
[1248] Calculated: C, 41.85; H, 5.13; N, 15.02; Cl, 4.75; S, 8.59
(%). Found: C, 41.86; H, 4.84; N, 15.06; Cl, 4.74; S, 8.48 (%).
EXAMPLE 136
[1249] 187
[1250] .sup.1H-NMR (D.sub.2O) .delta.: 1.32 (3H, d, J=6.9), 1.57
(2H, m), 2.08 (2H, m), 3.04 (1H, d, J=17.4 Hz), 3.15 (2H, m), 3.48
(1H, m), 4.14 (2H, m), 4.53 (1H, q, J=6.9 Hz), 4.74 (1H, d, J=15.0
Hz), 4.94 (1H, d, J=15.0 Hz), 5.12 (1H, d, J=4.8 Hz), 5.73 (1H, d,
J=4.8 Hz), 6.96 (2H, d, J=7.2 Hz), 8.02 (2H, d, J=7.2 Hz).
[1251] IR (KBr) cm.sup.-1: 3398, 1772, 1650, 1600, 1549, 1451,
1389, 1362, 1286, 1238, 1174, 1095, 1065, 1035.
[1252] MS (ESI): 665 (M+H).sup.+, 687 (M+Na).sup.+.
[1253] Elementary Analysis as
C.sub.26H.sub.29ClN.sub.8O.sub.7S.sub.2.mult- idot.4.3H.sub.2O.
[1254] Calculated: C, 42.05; H, 5.10; N, 15.09; Cl, 4.77; S, 8.64
(%). Found: C, 42.12; H, 5.16; N, 14.95; Cl, 4.68; S, 8.50 (%).
EXAMPLE 137
[1255] 188
[1256] .sup.1H-NMR (D.sub.2O) .delta.: 1.36 (3H, d, J=6.3 Hz), 1.45
(3H, d, J=6.6 Hz), 3.17 (1H, d, J=18.0 Hz), 3.57 (1H, d, J=18.0
Hz), 3.58-3.72 (3H, m), 4.65 (1H, q, J=6.6 Hz), 4.87 (1H, d, J=14.4
Hz), 5.09 (1H, d, J=14.4 Hz), 5.23 (1H, d, J=5.1 Hz), 5.86 (1H, d,
J=5.1 Hz), 6.93 (2H, d, J=6.9 Hz), 8.05-8.38 (2H, m).
[1257] IR (KBr) cm.sup.-1: 3294, 2983, 1774, 1650, 1592, 1555,
1456, 1395, 1360, 1287, 1218, 1167, 1092, 1065, 1034.
[1258] MS(ESI): 639.sup.+(M+H.sup.+).
[1259] Elementary Analysis as
C.sub.24H.sub.27ClN.sub.8O.sub.7S.sub.2.mult- idot.2.8H.sub.2O.
[1260] Calculated: C, 41.80; H, 4.77; N, 16.25; Cl, 5.14; S, 9.30
(%). Found: C, 41.83; H, 4.64; N, 16.29; Cl, 4.96; S, 9.22 (%).
EXAMPLE 138
[1261] 189
[1262] .sup.1H-NMR (D.sub.2O) .delta.: 1.35 (3H, d, J=6.3 Hz), 1.45
(3H, d, J=6.6 Hz), 1.82-2.13 (2H, m), 3.16 (1H, d, J=17.7 Hz),
3.35-3.50 (3H, m), 3.55 (1H, d, J=17.7 Hz), 4.65 (1H, q, J=6.6 Hz),
4.83 (1H, d, J=14.4 Hz), 5.05 (1H, d, J=14.4 Hz), 5.22 (1H, d,
J=4.2 Hz), 5.85 (1H, d, J=4.2 Hz), 6.83 (2H, d, J=6.3 Hz),
7.95-8.25 (2H, m).
[1263] IR (KBr) cm.sup.-1: 3415, 3067, 2982, 1772, 1650, 1597,
1557, 1447, 1395, 1360, 1288, 1216, 1169, 1094, 1065, 1034.
[1264] MS(FAB): 653.sup.+(M+H.sup.+).
[1265] Elementary Analysis as
C.sub.25H.sub.29ClN.sub.8O.sub.7S.sub.2.mult- idot.3.6H.sub.2O.
[1266] Calculated: C, 41.82; H, 5.08; N, 15.61; Cl, 4.94; S, 8.93
(%). Found: C, 41.89; H, 4.95; N, 15.54; Cl, 4.57; S, 8.60 (%).
EXAMPLE 139
[1267] 190
[1268] .sup.1H-NMR (D.sub.2O) .delta.: 1.40 (3H, d, J=6.6 Hz), 1.44
(3H, d, J=6.9 Hz), 2.88-3.02 (2H, m), 3.17 (1H, d, J=17.7 Hz), 3.63
(1H, d, J=17.7 Hz), 3.88 (1H, m), 4.66 (1H, q, J=6.9 Hz), 5.13 (1H,
d, J=14.7 Hz), 5.26 (1H, d, J=5.1 Hz), 5.40 (1H, d, J=14.4 Hz),
5.87 (1H, d, J=5.1 Hz), 8.07 (2H, d, J=7.2 Hz), 8.71 (2H, d, J=7.2
Hz).
[1269] IR (KBr) cm.sup.-1: 3388, 1775, 1716, 1607, 1537, 1517,
1464, 1394, 1328, 1287, 1182, 1159, 1101, 1066, 1035.
[1270] MS(FAB): 667 (M+H).sup.+, 1333 (2M+H).sup.+.
[1271] Elementary Analysis as
C.sub.25H.sub.27ClN.sub.8O.sub.8S.sub.2.mult- idot.3.7H.sub.2O.
[1272] Calculated: C, 40.92; H, 4.73; N, 15.27; Cl, 4.83; S, 8.74
(%). Found: C, 41.15; H, 4.46; N, 15.52; Cl, 4.57; S, 8.45 (%).
EXAMPLE 140
[1273] 191
[1274] .sup.1H-NMR (D.sub.2O) .delta.: 1.31 (3H, d, J=7.2 Hz), 1.52
(3H, d, J=6.9 Hz), 3.06 (1H, d, J=18.1 Hz), 3.50 (1H, d, J=18.1
Hz), 4.20 (1H, q, J=6.9 Hz), 4.52 (1H, q, J=7.2 Hz), 5.03 (1H, d,
J=14.4 Hz), 5.14 (1H, d, J=5.1 Hz), 5.29 (1H, d, J=14.4 Hz), 5.75
(1H, d, J=5.1 Hz), 8.00 (2H, d, J=7.2 Hz), 8.63 (2H, d, J=7.2
Hz).
[1275] IR (KBr) cm.sup.-1: 3398, 1775, 1730, 1612, 1538, 1516,
1466, 1397, 1356, 1327, 1288, 1197, 1158, 1110, 1066, 1035.
[1276] MS(ESI): 653 (M+H).sup.+.
[1277] Elementary Analysis as
C.sub.24H.sub.25ClN.sub.8O.sub.8S.sub.2.mult- idot.2.7H.sub.2O.
[1278] Calculated: C, 41.08; H, 4.37; N, 15.97; Cl, 5.05; S, 9.14
(%). Found: C, 41.13; H, 4.44; N, 15.94; Cl, 4.96; S, 8.94 (%).
EXAMPLE 141
[1279] 192
[1280] .sup.1H-NMR (D.sub.2O) .delta.: 1.44 (3H, d, J=7.5 Hz),
1.70-1.88 (1H, m), 1.98-2.20 (2H, m), 2.22-2.38 (1H, m), 3.17 (1H,
d, J=17.7 Hz), 3.30-3.42 (2H, m), 3.57 (1H, d, J=17.7 Hz), 3.70
(2H, d, J=6.3 Hz), 3.82-3.94 (1H, m), 4.66 (1H, q, J=7.5 Hz), 4.87
(1H, d, J=14.4 Hz), 5.10 (1H, d, J=14.4 Hz), 5.23 (1H, d, J=4.5
Hz), 5.85 (1H, d, J=4.5 Hz), 6.93 (2H, d, J=6.9 Hz), 8.05-8.30 (2H,
m).
[1281] IR (KBr) cm.sup.-1: 3398, 3065, 2983, 1774, 1650, 1602,
1556, 1447, 1394, 1360, 1287, 1218, 1168, 1096, 1064, 1034.
[1282] MS(FAB): 665.sup.+(M+H.sup.+).
[1283] Elementary Analysis as
C.sub.26H.sub.29ClN.sub.8O.sub.7S.sub.2.mult- idot.4.1H.sub.2O.
[1284] Calculated: C, 42.26; H, 5.07; N, 15.16; Cl, 4.80; S, 8.68
(%). Found: C, 42.29; H, 4.82; N, 15.26; Cl, 4.67; S, 8.53 (%).
EXAMPLE 142
[1285] 193
[1286] .sup.1H-NMR (D.sub.2O) .delta.: 1.44(3H, d, J=7.2 Hz),
2.73(3H, s), 3.17 and 3.38 (2H, ABq, J=18.0 Hz), 3.63(2H, t, J=6.0
Hz), 4.65(1H, q, J=7.2 Hz), 4.80(2H, t, J=6.0 Hz), 5.17(1H, d,
J=4.8 Hz), 5.56 and 5.69(2H, ABq, J=15.0 Hz), 5.85(1H, d, J=4.8
Hz), 7.09(1H, d, J=3.3 Hz), 7.73(1H, dd, J=6.3 and 8.4 Hz),
8.15(1H, d, J=3.3 Hz), 8.62(1H, d, J=8.4 Hz), 8.68(1H, d, J=6.3
Hz).
[1287] IR (KBr) cm.sup.-1: 3407, 2452, 1773, 1603, 1539, 1500,
1467, 1392, 1364, 1287, 1184, 1120, 1089, 1063, 1032.
[1288] MS(FAB): 663.sup.+(M+H.sup.+).
[1289] Elementary Analysis as
C.sub.26H.sub.27ClN.sub.8O.sub.7S.sub.2.mult- idot.5.2H.sub.2O.
[1290] Calculated: C, 41.26; H, 4.98; N, 14.81; Cl, 4.68; S, 8.47
(%). Found: C, 41.41; H, 4.90; N, 14.55; Cl, 4.54; S, 8.46 (%).
[1291] Quaternary Salt Ester: 194
[1292] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.04(9H, brs), 1.43(3H,
d, =7.2 Hz), 1.46(9H, s), 2.78(3H, brs), 3.21 and 3.40(2H, Abq,
J=18.6 Hz), 3.60(2H, m), 3.76(3H, s), 4.60(2H, t-like), 4.89(1H, q,
J=7.2 Hz), 5.20(1H, d, J=5.1 Hz), 5.23 and 5.31(2H, Abq, J=11.7
Hz), 5.71(2H, brs), 5.97(1H, dd, J=5.1 and 8.7 Hz), 6.82(1H, s),
6.92(2H, d, J=8.7 Hz), 7.01(1H, d, J=3.3 Hz), 7.22-7.42(12H, m),
7.83(1H, brs), 8.30(1H, d, J=3.3 Hz), 8.65(1H, brs), 8.84(1H, brs),
9.77(1H, d, J=8.7 Hz), 12.1(brs).
[1293] IR (KBr) cm.sup.-1: 3422, 3061, 3032, 2977, 2935, 1791,
1717, 1690, 1631, 1613, 1584, 1550, 1515, 1495, 1455, 1392, 1367,
1248, 1155, 1118, 1100, 1065, 1032, 1018.
[1294] MS(FAB):
1149.sup.+(C.sub.57H.sub.62ClN.sub.8O.sub.12S.sub.2.sup.+)- .
EXAMPLE 143
[1295] 195
[1296] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.2 Hz), 3.21
and 3.35 (2H, ABq, J=18.0 Hz), 4.64(1H, q, J=7.2 Hz), 5.01(2H, s),
5.17(1H, d, J=4.8 Hz), 5.53 and 5.74(2H, ABq, J=15.0 Hz), 5.89(1H,
d, J=4.8 Hz), 6.98(1H, d, J=3.3 Hz), 7.67(1H, dd, J=6.3 and 8.1
Hz), 8.04(1H, d, J=3.3 Hz), 8.44(1H, d, J=8.1 Hz), 8.62(1H, d,
J=6.3 Hz).
[1297] IR (KBr) cm.sup.-1: 3415, 2989, 2527, 1778, 1725, 1672,
1630, 1537, 1500, 1467, 1373, 1328, 1229, 1162, 1129, 1063,
1035.
[1298] MS(ESI): 664.sup.+(M+H.sup.+).
[1299] Elementary Analysis as
C.sub.25H.sub.22ClN.sub.7O.sub.9S.sub.2.mult- idot.3.0H.sub.2O.
[1300] Calculated: C, 41.81; H, 3.93; N, 13.65; Cl, 4.94; S, 8.93
(%). Found: C, 41.75; H, 3.89; N, 13.71; Cl, 5.08; S, 8.84 (%).
[1301] Quaternary Salt Ester: 196
[1302] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.42(3H, d, J=7.2 Hz),
1.44(9H, s), 1.46(9H, s), 3.37(2H, brs), 3.75(3H, s), 4.89(1H, q,
J=7.2 Hz), 5.20(1H, d, J=5.1 Hz), 5.21 and 5.29(2H, Abq, J=12.0
Hz), 5.38(2H, brs), 5.72(2H, brs), 5.96(1H, dd, J=5.1 and 8.7 Hz),
6.82(1H, s), 6.89(2H, d, J=8.7 Hz), 7.00(1H, d, J=3.3 Hz),
7.22-7.42(12H, m), 7.80(1H, dd, J=6.3 and 8.4 Hz), 8.31(1H, d,
J=3.3 Hz), 8.62(1H, d, J=6.3 Hz), 8.82(1H, d, J=8.4 Hz), 9.76(1H,
d, J=8.7 Hz), 12.1(brs).
[1303] IR (KBr) cm.sup.-1: 3422, 3061, 3031, 2979, 2935, 1790,
1738, 1631, 1613, 1585, 1550, 1515, 1498, 1466, 1455, 1392, 1369,
1329, 1247, 1155, 1128, 1100, 1064, 1032.
[1304] MS(FAB):
1106.sup.+(C.sub.55H.sub.57ClN.sub.7O.sub.12S.sub.2.sup.+)- .
EXAMPLE 144
[1305] 197
[1306] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=6.9 Hz), 3.20
and 3.37 (2H, ABq, J=17.7 Hz), 4.64(1H, q, J=6.9 Hz), 5.17(1H, d,
J=4.8 Hz), 5.27(2H, s), 5.56 and 5.73(2H, ABq, J=15.0 Hz), 5.88(1H,
d, J=4.8 Hz), 7.06(1H, d, J=3.3 Hz), 7.70(1H, dd, J=6.3 and 8.1
Hz), 8.07(1H, d, J=3.3 Hz), 8.51(1H, d, J=8.1 Hz), 8.67(1H, d,
J=6.3 Hz).
[1307] IR (KBr) cm.sup.-1: 3407, 3191, 2988, 1776, 1684, 1615,
1537, 1500, 1467, 1364, 1331, 1225, 1189, 1160, 1131, 1063,
1034.
[1308] MS(ESI): 663.sup.+(M+H.sup.+).
[1309] Elementary Analysis as
C.sub.25H.sub.23ClN.sub.8O.sub.8S.sub.2.mult- idot.3.9H.sub.2O.
[1310] Calculated: C, 40.95; H, 4.23; N, 15.28; Cl, 4.83; S, 8.74
(%). Found: C, 40.93; H, 4.06; N, 15.26; Cl, 4.82; S, 8.64 (%).
[1311] Quaternary Salt Ester: 198
[1312] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.45(3H, d, J=6.9 Hz),
1.46(9H, s), 3.39(2H, brs), 3.75(3H, s), 4.89(1H, q, J=6.9 Hz),
5.17(2H, brs), 5.20(1H, d, J=4.8 Hz), 5.21 and 5.29(2H, Abq, J=11.7
Hz), 5.70(2H, brs), 5.96(1H, dd, J=4.8 and 8.7 Hz), 6.82(1H, s),
6.89(2H, d, J=8.7 Hz), 6.96(1H, d, J=3.3 Hz), 7.20-7.45(12H, m),
7.76(1H, dd, J=6.0 and 8.7 Hz), 7.79(2H, brs), 8.29(1H, d, J=3.3
Hz), 8.58(1H, d, J=6.0 Hz), 8.73(1H, d, J=8.7 Hz), 9.76(1H, d,
J=8.7 Hz), 12.1(brs).
[1313] IR (KBr) cm.sup.-1: 3422, 3063, 2980, 2936, 1789, 1716,
1690, 1631, 1613, 1585, 1551, 1515, 1497, 1467, 1455, 1393, 1369,
1248, 1175, 1154, 1128, 1100, 1065, 1030, 1018.
[1314] MS(FAB):
1049.sup.+(C.sub.51H.sub.50ClN.sub.8O.sub.11S.sub.2.sup.+)- .
EXAMPLE 145
[1315] 199
[1316] .sup.1H-NMR (D.sub.2O) .delta.: 1.44(3H, d, J=7.2 Hz), 3.20
and 3.37 (2H, ABq, J=17.7 Hz), 3.73(3H, s), 4.65(1H, q, J=7.2 Hz),
5.17(2H, s), 5.18(1H, d, J=4.8 Hz), 5.56 and 5.73(2H, ABq, J=15.0
Hz), 5.88(1H, d, J=4.8 Hz), 7.06(1H, d, J=3.3 Hz), 7.71(1H, dd,
J=6.3 and 8.1 Hz), 8.08(1H, d, J=3.3 Hz), 8.53(1H, d, J=8.1 Hz),
8.68(1H, d, J=6.3 Hz).
[1317] IR (KBr) cm.sup.-1: 3422, 2985, 2938, 1778, 1678, 1615,
1537, 1501, 1466, 1442, 1365, 1330, 1225, 1188, 1159, 1129, 1065,
1034.
[1318] MS(FAB): 693.sup.+(M+H.sup.+).
[1319] Elementary Analysis as
C.sub.26H.sub.25ClN.sub.8O.sub.9S.sub.2.mult- idot.3.9H.sub.2O.
[1320] Calculated: C, 40.91; H, 4.33; N, 14.68; Cl, 4.64; S, 8.40
(%). Found: C, 40.78; H, 4.14; N, 14.77; Cl, 4.67; S, 8.54 (%).
[1321] Quaternary Salt Ester: 200
[1322] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.44(3H, d, J=7.2 Hz),
1.46(9H, s), 3.39(2H, brs), 3.68(3H, s), 3.76(3H, s), 4.89(1H, q,
J=7.2 Hz), 5.14(2H, brs), 5.20(1H, d, J=4.8 Hz), 5.21 and 5.28(2H,
Abq, J=11.4 Hz), 5.71(2H, brs), 5.96(1H, dd, J=4.8 and 8.7 Hz),
6.82(1H, s), 6.88(2H, d, J=8.7 Hz), 6.98(1H, d, J=3.0 Hz),
7.20-7.41(13H, m), 7.80(1H, dd, J=6.0 and 8.1 Hz), 8.30(1H, d,
J=3.0 Hz), 8.59(1H, d, J=6.0 Hz), 8.76(1H, d, J=8.1 Hz), 9.76(1H,
d, J=8.7 Hz), 12.1(brs).
[1323] IR (KBr) cm.sup.-1: 3428, 3101, 3063, 3031, 2980, 2937,
1789, 1717, 1632, 1613, 1585, 1550, 1515, 1497, 1466, 1391, 1369,
1326, 1247, 1175, 1155, 1127, 1100, 1064, 1032, 1018.
[1324] MS(FAB):
1079.sup.+(C.sub.52H.sub.52ClN.sub.8O.sub.12S.sub.2.sup.+)- .
EXAMPLE 146
[1325] 201
[1326] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.2 Hz), 3.19
and 3.37 (2H, ABq, J=17.4 Hz), 4.65(1H, q, J=7.2 Hz), 5.17(1H, d,
J=4.8 Hz), 5.19(2H, s), 5.56 and 5.72(2H, ABq, J=15.0 Hz), 5.87(1H,
d, J=4.8 Hz), 7.06(1H, d, J=3.3 Hz), 7.71(1H, dd, J=6.0 and 8.1
Hz), 8.08(1H, d, J=3.3 Hz), 8.52(1H, d, J=8.1 Hz), 8.68(1H, d,
J=6.0 Hz).
[1327] IR (KBr) cm.sup.-1:3415, 2988, 1777, 1675, 1615, 1537, 1500,
1466, 1365, 1330, 1225, 1188, 1161, 1129, 1064, 1036.
[1328] MS(FAB): 679.sup.+(M+H.sup.+).
[1329] Elementary Analysis as
C.sub.25H.sub.23ClN.sub.8O.sub.9S.sub.2.mult- idot.3.5H.sub.2O.
[1330] Calculated: C, 40.46; H, 4.07; N, 15.10; Cl, 4.78; S, 8.64
(%). Found: C, 40.45; H, 4.00; N, 15.08; Cl, 4.72; S, 8.57 (%).
[1331] Quaternary Salt Ester: 202
[1332] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.45(3H, d, J=7.2 Hz),
1.46(9H, s), 3.40(2H, brs), 3.75(6H, s), 4.74(2H, brs), 4.89(1H, q,
J=7.2 Hz), 5.13(2H, brs), 5.20(1H, d, J=5.1 Hz), 5.21 and 5.28(2H,
Abq, J=12.0 Hz), 5.71(2H, brs), 5.96(1H, dd, J=5.1 and 8.7 Hz),
6.82(1H, s), 6.89(2H, d, J=8.7 Hz), 6.99(1H, d, J=3.3 Hz),
7.19-7.49(13H, m), 7.79(1H, dd, J=6.3 and 8.7 Hz), 8.29(1H, d,
J=3.3 Hz), 8.61(1H, d, J=6.3 Hz), 8.71(1H, d, J=8.7 Hz), 9.76(1H,
d, J=8.7 Hz), 12.1(brs).
[1333] IR (KBr) cm.sup.-1: 3421, 3063, 2978, 2936, 2836, 1790,
1716, 1631, 1612, 1585, 1549, 1514, 1497, 1465, 1369, 1325, 1248,
1176, 1154, 1125, 1100, 1064, 1030.
[1334] MS(FAB):
1185.sup.+(C.sub.59H.sub.58ClN.sub.8O.sub.13S.sub.2.sup.+)- .
EXAMPLE 147
[1335] 203
[1336] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.2 Hz), 3.18
and 3.34 (2H, ABq, J=18.0 Hz), 3.97(2H, t, J=4.8 Hz), 4.54(2H, t,
J=4.8 Hz), 4.64(1H, q, J=7.2 Hz), 5.16(1H, d, J=4.8 Hz), 5.53 and
5.71(2H, ABq, J=15.0 Hz), 5.87(1H, d, J=4.8 Hz), 7.00(1H, d, J=3.0
Hz), 7.67(1H, dd, J=6.3 and 8.1 Hz), 8.12(1H, d, J=3.0 Hz),
8.59(1H, d, J=8.1 Hz), 8.62(1H, d, J=6.3 Hz).
[1337] IR (KBr) cm.sup.-1: 3408, 2938, 1776, 1670, 1615, 1539,
1496, 1466, 1447, 1362, 1322, 1240, 1187, 1159, 1130, 1072,
1034.
[1338] MS(FAB): 650.sup.+(M+H.sup.+).
[1339] Elementary Analysis as
C.sub.25H.sub.24ClN.sub.7O.sub.8S.sub.2.mult- idot.4.1H.sub.2O.
[1340] Calculated: C, 41.48; H, 4.48; N, 13.54; Cl, 4.90; S, 8.86
(%). Found: C, 41.48; H, 4.40; N, 13.59; Cl, 5.07; S, 8.88 (%).
EXAMPLE 148
[1341] 204
[1342] .sup.1H-NMR (D.sub.2O) .delta.: 1.44(3H, d, J=6.9 Hz), 3.16
and 3.31 (2H, ABq, J=18.0 Hz), 4.43(2H, t, J=4.5 Hz), 4.65(1H, q,
J=6.9 Hz), 4.68(2H, t, J=4.5 Hz), 5.17(1H, d, J=5.1 Hz), 5.54 and
5.71(2H, ABq, J=15.0 Hz), 5.87(1H, d, J=5.1 Hz), 7.01(1H, d, J=3.0
Hz), 7.69(1H, dd, J=6.3 and 8.1 Hz), 8.12(1H, d, J=3.0 Hz),
8.61(1H, d, J=8.1 Hz), 8.63(1H, d, J=6.3 Hz).
[1343] IR (KBr) cm.sup.-1: 3415, 3193, 2987, 1777, 1718, 1673,
1614, 1537, 1497, 1466, 1447, 1364, 1328, 1225, 1188, 1135, 1080,
1034.
[1344] MS(FAB): 693.sup.+(M+H.sup.+).
[1345] Elementary Analysis as
C.sub.26H.sub.25ClN.sub.8O.sub.9S.sub.2.mult- idot.3.0H.sub.2O.
[1346] Calculated: C, 41.80; H, 4.18; N, 15.00; Cl, 4.75; S, 8.58
(%). Found: C, 41.68; H, 4.19; N, 14.79; Cl, 4.78; S, 8.91 (%).
EXAMPLE 149
[1347] 205
[1348] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.2 Hz), 3.15
and 3.31(2H, ABq, J=17.7 Hz), 3.47(3H, s), 4.54(2H, t, J=4.8 Hz),
4.64(1H, q, J=7.2 Hz), 4.72(2H, t, J=4.8 Hz), 5.17(1H, d, J=4.8
Hz), 5.54 and 5.71(2H, ABq, J=15.0 Hz), 5.87(1H, d, J=4.8 Hz),
7.02(1H, d, J=3.3 Hz), 7.71(1H, dd, J=6.3 and 8.4 Hz), 8.13(1H, d,
J=3.3 Hz), 8.62(1H, d, J=8.4 Hz), 8.64(1H, d, J=6.3 Hz).
[1349] IR (KBr) cm.sup.-1: 3416, 2984, 2939, 1778, 1731, 1674,
1615, 1538, 1498, 1466, 1445, 1364, 1326, 1286, 1264, 1189, 1123,
1035.
[1350] MS(FAB): 723.sup.+(M+H.sup.+).
[1351] Elementary Analysis as
C.sub.27H.sub.27ClN.sub.8O.sub.10S.sub.2.mul-
tidot.3.7H.sub.2O.
[1352] Calculated: C, 41.06; H, 4.39; N, 14.19; Cl, 4.49; S, 8.12
(%). Found: C, 40.93; H, 4.29; N, 14.32; Cl, 4.63; S, 8.14 (%).
EXAMPLE 150
[1353] 206
[1354] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.2 Hz),
2.45(3H, s), 3.15 and 3.31(2H, ABq, J=17.7 Hz), 4.44(2H, brs),
4.64(1H, q, J=7.2 Hz), 4.69(2H, brs), 5.17(1H, d, J=4.8 Hz), 5.54
and 5.71(2H, ABq, J=15.3 Hz), 5.87(1H, d, J=4.8 Hz), 7.01(1H, d,
J=3.0 Hz), 7.69(1H, dd, J=6.0 and 8.4 Hz), 8.11(1H, d, J=3.0 Hz),
8.60(1H, d, J=8.4 Hz), 8.64(1H, d, J=6.0 Hz).
[1355] IR (KBr) cm.sup.-1: 3401, 2984, 1779, 1710, 1676, 1617,
1538, 1498, 1466, 1364, 1326, 1265, 1187, 1135, 1097, 1033.
[1356] MS(FAB): 707.sup.+(M+H.sup.+).
[1357] Elementary Analysis as
C.sub.27H.sub.27ClN.sub.8O.sub.9S.sub.2.mult- idot.3.5H.sub.2O.
[1358] Calculated: C, 42.11; H, 4.45; N, 14.55; Cl, 4.60; S, 8.33
(%). Found: C, 42.18; H, 4.37; N, 14.52; Cl, 4.63; S, 8.12 (%).
EXAMPLE 151
[1359] 207
[1360] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.2 Hz),
2.66(3H, s), 2.70(3H, s), 3.14 and 3.30(2H, ABq, J=17.7 Hz),
4.46(2H, t, J=4.8 Hz), 4.64(1H, q, J=7.2 Hz), 4.72(2H, t, J=4.8
Hz), 5.17(1H, d, J=5.1 Hz), 5.55 and 5.71(2H, ABq, J=15.3 Hz),
5.87(1H, d, J=5.1 Hz), 7.02(1H, d, J=3.3 Hz), 7.70(1H, dd, J=6.6
and 8.1 Hz), 8.15(1H, d, J=3.3 Hz), 8.64(1H, d, J=8.1 Hz), 8.65(1H,
d, J=6.6 Hz).
[1361] IR (KBr) cm.sup.-1: 3422, 2938, 1779, 1690, 1617, 1538,
1497, 1466, 1363, 1325, 1287, 1190, 1135, 1098, 1066, 1034.
[1362] MS(FAB): 721.sup.+(M+H.sup.+).
[1363] Elementary Analysis as
C.sub.28H.sub.29ClN.sub.8O.sub.9S.sub.2.mult- idot.3.5H.sub.2O.
[1364] Calculated: C, 42.88; H, 4.63; N, 14.29; Cl, 4.52; S, 8.18
(%). Found: C, 42.81; H, 4.62; N, 14.23; Cl, 4.50; S, 8.38 (%).
EXAMPLE 152
[1365] 208
[1366] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.2 Hz), 3.17
and 3.32(2H, ABq, J=17.7 Hz), 4.52(2H, t, J=4.8 Hz), 4.65(1H, q,
J=7.2 Hz), 4.71(2H, t, J=4.8 Hz), 5.17(1H, d, J=4.8 Hz), 5.53 and
5.71(2H, ABq, J=15.0 Hz), 5.87(1H, d, J=4.8 Hz), 7.00(1H, d, J=3.3
Hz), 7.70(1H, dd, J=6.0 and 8.4 Hz), 8.11(1H, d, J=3.3 Hz),
8.61(1H, d, J=8.4 Hz), 8.63(1H, d, J=6.0 Hz).
[1367] IR (KBr) cm.sup.-1: 3307, 2938, 1777, 1728, 1673, 1613,
1537, 1498, 1466, 1364, 1326, 1285, 1188, 1122, 1034.
[1368] MS(FAB): 709.sup.+(M+H.sup.+).
[1369] Elementary Analysis as
C.sub.26H.sub.25ClN.sub.8O.sub.10S.sub.2.mul-
tidot.3.5H.sub.2O.
[1370] Calculated: C, 40.44; H, 4.18; N, 14.51; Cl, 4.59; S, 8.31
(%). Found: C, 40.45; H, 4.15; N, 14.48; Cl, 4.70; S, 8.41 (%).
EXAMPLE 153
[1371] 209
[1372] .sup.1H-NMR (D.sub.2O) .delta.: 1.44(3H, d, J=7.2 Hz),
2.33(6H, s), 3.17 and 3.33(2H, ABq, J=17.7 Hz), 4.48(2H, brs),
4.65(1H, q, J=7.2 Hz), 4.69(2H, brs), 5.18(1H, d, J=4.8 Hz), 5.54
and 5.71(2H, ABq, J=14.7 Hz), 5.87(1H, d, J=4.8 Hz), 7.03(1H, d,
J=3.3 Hz), 7.72(1H, dd, J=6.0 and 8.7 Hz), 8.13(1H, d, J=3.3 Hz),
8.60(1H, d, J=8.7 Hz), 8.64(1H, d, J=6.0 Hz).
[1373] IR (KBr) cm.sup.-1: 3412, 2900, 2960, 1779, 1723, 1671,
1626, 1541, 1498, 1466, 1449, 1427, 1364, 1326, 1286, 1244, 1187,
1163, 1135, 1114, 1035.
[1374] MS(FAB): 636.sup.+(M+H.sup.+).
[1375] Elementary Analysis as
C.sub.28H.sub.30ClN.sub.9O.sub.9S.sub.2.mult- idot.4.2H.sub.2O.
[1376] Calculated: C, 41.42; H, 4.77; N, 15.53; Cl, 4.37; S, 7.90
(%). Found: C, 41.36; H, 4.55; N, 15.46; Cl, 4.36; S, 8.17 (%).
EXAMPLE 154
[1377] 210
[1378] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=6.9 Hz), 3.17
and 3.33(2H, ABq, J=17.7 Hz), 3.62(3H, s), 4.29(2H, t, J=4.8 Hz),
4.64(1H, q, J=6.9 Hz), 4.69(2H, t, J=4.8 Hz), 5.17(1H, d, J=4.5
Hz), 5.54 and 5.72(2H, ABq, J=15.0 Hz), 5.87(1H, d, J=4.5 Hz),
7.02(1H, d, J=3.3 Hz), 7.68(1H, dd, J=6.3 and 8.4 Hz), 8.18(1H, d,
J=3.3 Hz), 8.61(1H, d, J=8.4 Hz), 8.63(1H, d, J=6.3 Hz).
[1379] IR (KBr) cm.sup.-1: 3415, 2988, 2953, 1778, 1674, 1616,
1538, 1498, 1466, 1363, 1321, 1285, 1190, 1132, 1062, 1035.
[1380] MS(FAB): 723.sup.+(M+H.sup.+).
[1381] Elementary Analysis as
C.sub.27H.sub.27ClN.sub.8O.sub.10S.sub.2.mul-
tidot.4.1H.sub.2O.
[1382] Calculated: C, 40.69; H, 4.45; N, 14.06; Cl, 4.45; S, 8.05
(%). Found: C, 40.47; H, 4.28; N, 14.18; Cl, 4.88; S, 8.56 (%).
EXAMPLE 155
[1383] 211
[1384] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=6.9 Hz),
1.74(3H, s), 3.18 and 3.33(2H, ABq, J=17.7 Hz), 3.62(2H, t, J=5.4
Hz), 4.53(2H, t, J=5.4 Hz), 4.65(1H, q, J=6.9 Hz), 5.18(1H, d,
J=4.8 Hz), 5.53 and 5.71(2H, ABq, J=14.7 Hz), 5.87(1H, d, J=4.8
Hz), 6.99(1H, d, J=3.0 Hz), 7.69(1H, dd, J=6.3 and 8.4 Hz),
8.07(1H, d, J=3.0 Hz), 8.57(1H, d, J=8.4 Hz), 8.62(1H, d, J=6.3
Hz).
[1385] IR (KBr) cm.sup.-1: 3400, 2938, 1777, 1629, 1540, 1497,
1467, 1450, 1368, 1323, 1288, 1240, 1189, 1159, 1134, 1095,
1035.
[1386] MS(FAB): 691.sup.+(M+H.sup.+).
[1387] Elementary Analysis as
C.sub.27H.sub.27ClN.sub.8O.sub.8S.sub.2.mult- idot.4.1H.sub.2O.
[1388] Calculated: C, 41.51; H, 4.77; N, 14.34; Cl, 4.54; S, 8.21
(%). Found: C, 41.33; H, 4.56; N, 14.36; Cl, 4.88; S, 8.39 (%).
EXAMPLE 156
[1389] 212
[1390] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.5 Hz), 3.15
and 3.32(2H, ABq, J=17.7 Hz), 3.91(3H, s), 3.57(2H, brs), 4.51(2H,
m), 4.65(1H, q, J=7.5 Hz), 5.17(1H, d, J=4.8 Hz), 5.55 and 5.70(2H,
ABq, J=14.7 Hz), 5.87(1H, d, J=4.8 Hz), 7.00(1H, d, J=3.3 Hz),
7.69(1H, dd, J=6.0 and 8.1 Hz), 8.09(1H, d, J=3.3 Hz), 8.59(1H, d,
J=8.1 Hz), 8.64(1H, d, J=6.0 Hz).
[1391] IR (KBr) cm.sup.-1: 3410, 2987, 2940, 1777, 1677, 1626,
1537, 1499, 1466, 1365, 1322, 1271, 1191, 1157, 1132, 1096,
1035.
[1392] MS(FAB): 07.sup.+(M+H.sup.+).
[1393] HR-MS(FAB): calcd for
C.sub.27H.sub.28ClN.sub.8O.sub.9S.sub.2 707.1109 found
707.1106.
EXAMPLE 157
[1394] 213
[1395] .sup.1H-NMR (D.sub.2O) .delta.: 1.44(3H, d, J=6.9 Hz), 3.18
and 3.33(2H, ABq, J=17.7 Hz), 3.54(2H, t, J=4.5 Hz), 4.49(2H, t,
J=4.5 Hz), 4.65(1H, q, J=6.9 Hz), 5.17(1H, d, J=5.1 Hz), 5.52 and
5.70(2H, ABq, J=15.0 Hz), 5.87(1H, d, J=5.1 Hz), 6.98(1H, d, J=3.3
Hz), 7.67(1H, dd, J=6.3 and 8.1 Hz), 8.07(1H, d, J=3.3 Hz),
8.55(1H, d, J=8.1 Hz), 8.60(1H, d, J=6.3 Hz).
[1396] IR (KBr) cm.sup.-1: 3375, 1773, 1660, 1609, 1543, 1497,
1466, 1451, 1362, 1288, 1240, 1188, 1159, 1133, 1098, 1035.
[1397] MS(FAB): 692.sup.+(M+H.sup.+).
[1398] HR-MS(FAB): calcd for
C.sub.26H.sub.27ClN.sub.9O.sub.8S.sub.2 692.1113 found
692.1100.
[1399] Elementary Analysis as
C.sub.26H.sub.26ClN.sub.9O.sub.8S.sub.2.mult- idot.4.3H.sub.2O.
[1400] Calculated: C, 40.58; H, 4.53; N, 16.38; Cl, 4.61; S, 8.33
(%). Found: C, 40.46; H, 4.38; N, 16.84; Cl, 5.26; S, 7.73 (%).
EXAMPLE 158
[1401] 214
[1402] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.2 Hz), 3.14
and 3.31(2H, ABq, J=17.7 Hz), 3.53(2H, t-like), 4.57(2H, t-like),
4.64(1H, q, J=7.2 Hz), 5.17(1H, d, J=4.8 Hz), 5.54 and 5.70(2H,
ABq, J=15.0 Hz), 5.87(1H, d, J=4.8 Hz), 7.00(1H, d, J=3.3 Hz),
7.68(1H, dd, J=6.3 and 8.4 Hz), 8.13(1H, d, J=3.3 Hz), 8.62(1H, d,
J=8.4 Hz), 8.62(1H, d, J=6.3 Hz).
[1403] IR (KBr) cm.sup.-1: 3316, 1775, 1671, 1611, 1538, 1497,
1467, 1448, 1363, 1326, 1241, 1157, 1134, 1097, 1035.
[1404] MS(FAB): 728.sup.+(M+H.sup.+).
[1405] Elementary Analysis as
C.sub.25H.sub.26ClN.sub.9O.sub.9S.sub.3.mult- idot.3.6H.sub.2O.
[1406] Calculated: C, 37.86; H, 4.22; N, 15.90; Cl, 4.47; S, 12.13
(%). Found: C, 37.88; H, 4.10; N, 15.92; Cl, 4.37; S, 12.00
(%).
[1407] IR (KBr) cm.sup.-1: 3316, 1775, 1671, 1611, 1538, 1497,
1467, 1448, 1363, 1326, 1241, 1157, 1134, 1097, 1035.
[1408] MS(FAB): 728.sup.+(M+H.sup.+).
[1409] Elementary Analysis as
C.sub.25H.sub.26ClN.sub.9O.sub.9S.sub.3.mult- idot.3.6H.sub.2O.
[1410] Calculated: C, 37.86; H, 4.22; N, 15.90; Cl, 4.47; S, 12.13
(%). Found: C, 37.88; H, 4.10; N, 15.92; Cl, 4.37; S, 12.00
(%).
EXAMPLE 159
[1411] 215
[1412] .sup.1H-NMR (D.sub.2O) .delta.: 1.44(3H, d, J=6.9 Hz),
2.25(2H, m), 3.17 and 3.33(2H, ABq, J=17.7 Hz), 3.95(2H, t, J=5.7
Hz), 4.54(2H, t, J=6.3 Hz), 4.65(1H, q, J=6.9 Hz), 5.17(1H, d,
J=5.1 Hz), 5.53 and 5.70(2H, ABq, J=15.0 Hz), 5.87(1H, d, J=5.1
Hz), 7.00(1H, d, J=3.3 Hz), 7.67(1H, dd, J=6.3 and 8.4 Hz),
8.12(1H, d, J=3.3 Hz), 8.59(1H, d, J=8.4 Hz), 8.61(1H, d, J=6.3
Hz).
[1413] IR (KBr) cm.sup.-1:3402, 3193, 2985, 1777, 1710, 1673, 1612,
1539, 1497, 1457, 1362, 1331, 1239, 1189, 1132, 1103, 1078,
1036.
[1414] MS(FAB): 707.sup.+(M+H.sup.+).
[1415] Elementary Analysis as
C.sub.27H.sub.27ClN.sub.8O.sub.9S.sub.2.mult- idot.3.4H.sub.2O.
[1416] Calculated: C, 42.20; H, 4.43; N, 14.58; Cl, 4.61; S, 8.35
(%). Found: C, 42.19; H, 4.34; N, 14.60; Cl, 4.54; S, 8.23 (%).
EXAMPLE 160
[1417] 216
[1418] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.2 Hz),
2.26-2.42(4H, m), 3.15 and 3.34(2H, ABq, J=17.7 Hz), 3.28(2H, dt,
J=3.0 and 12.6 Hz), 3.64(2H, d, J=12.6 Hz), 4.65(1H, q, J=7.2 Hz),
4.91-5.00(1H, m), 5.16(1H, d, J=4.8 Hz), 5.55 and 5.69(2H, ABq,
J=15.0 Hz), 5.85(1H, d, J=4.8 Hz), 7.06(1H, d, J=3.6 Hz), 7.69(1H,
dd, J=6.3 and 8.4 Hz), 8.23(1H, d, J=3.6 Hz), 8.64(1H, d, J=8.4
Hz), 8.65(1H, d, J=6.3 Hz).
[1419] IR (KBr) cm.sup.-1:3397, 2528, 1773, 1599, 1539, 1494, 1461,
1396, 1360, 1315, 1285, 1185, 1128, 1068, 1032.
[1420] MS(FAB): 689.sup.+(M+H.sup.+).
[1421] Elementary Analysis as
C.sub.28H.sub.29ClN.sub.8O.sub.7S.sub.2.mult- idot.6.5H.sub.2O.
[1422] Calculated: C, 41.71; H, 5.25; N, 13.90; Cl, 4.40; S, 7.95
(%). Found: C, 41.69; H, 5.13; N, 13.96; Cl, 4.35; S, 7.78 (%).
EXAMPLE 161
[1423] 217
[1424] .sup.1H-NMR (D.sub.2O) .delta.: 1.36(3H, d, J=6.9 Hz),
1.43(3H, d, J=7.2 Hz), 2.10-2.37(2H, m), 3.16 and 3.36(2H, ABq,
J=17.7 Hz), 3.31-3.42(1H, m), 4.52(2H, t-like), 4.65(1H, q, J=7.2
Hz), 5.17(1H, d, J=4.8 Hz), 5.54 and 5.69(2H, ABq, J=15.0 Hz),
5.85(1H, d, J=4.8 Hz), 7.02(1H, d, J=3.3 Hz), 7.69(1H, dd, J=6.0
and 8.7 Hz), 8.14(1H, d, J=3.3 Hz), 8.59(1H, d, J=8.7 Hz), 8.63(1H,
d, J=6.0 Hz).
[1425] IR (KBr) cm.sup.-1: 3388, 2981, 1775, 1591, 1539, 1499,
1458, 1393, 1363, 1286, 1221, 1186, 1160, 1114, 1062, 1033.
[1426] MS(FAB): 677.sup.+(M+H.sup.+).
[1427] Elementary Analysis as
C.sub.27H.sub.29ClN.sub.8O.sub.7S.sub.2.mult- idot.5.4H.sub.2O.
[1428] Calculated: C, 41.87; H, 5.18; N, 14.47; Cl, 4.58; S,
8.28(%). Found: C, 41.81; H, 4.96; N, 14.40; Cl, 4.69; S, 8.30
(%).
EXAMPLE 162
[1429] 218
[1430] .sup.1H-NMR (D.sub.2O) .delta.: 1.42(3H, d, J=6.9 Hz),
2.30(1H, m), 2.54(1H, m), 3.19 and 3.33(2H, ABq, J=18.0 Hz),
3.42-3.59(2H, m), 3.72-3.78(1H, m), 3.88-3.94(1H, m), 4.63(1H, q,
J=6.9 Hz), 5.18(1H, d, J=4.8 Hz), 5.36(1H, m), 5.53 and 5.72(2H,
ABq, J=15.3 Hz), 5.82(1H, d, J=4.8 Hz), 7.00(1H, d, J=3.6 Hz),
7.69(1H, dd, J=6.0 and 8.4 Hz), 8.08(1H, d, J=3.6 Hz), 8.62(1H, d,
J=6.0 Hz), 8.63(1H, d, J=8.4 Hz).
[1431] IR (KBr) cm.sup.-1: 3387, 1770, 1667, 1605, 1543, 1495,
1461, 1399, 1359, 1321, 1285, 1202, 1149, 1131, 1081, 1058,
1029.
[1432] MS(ESI): 675.sup.+(M+H.sup.+).
[1433] Elementary Analysis as
C.sub.27H.sub.27ClN.sub.8O.sub.7S.sub.2.mult-
idot.6.0H.sub.2O.multidot.0.2(C.sub.3H.sub.7OH).
[1434] Calculated: C, 41.68; H, 5.15; N, 14.09; Cl, 4.46; S, 8.06
(%). Found: C, 41.53; H, 5.05; N, 14.16; Cl, 4.35; S, 7.82 (%).
EXAMPLE 163
[1435] 219
[1436] .sup.1H-NMR (D.sub.2O) .delta.: 1.44(3H, d, J=7.2 Hz),
2.30(1H, m), 2.53(1H, m), 3.19 and 3.33(2H, ABq, J=17.7 Hz),
3.42-3.59(2H, m), 3.72-3.78(1H, m), 3.88-3.94 (1H, m), 4.66(1H, q,
J=7.2 Hz), 5.18(1H, d, J=5.1 Hz), 5.38(1H, m), 5.52 and 5.71(2H,
ABq, J=15.0 Hz), 5.87(1H, d, J=5.1 Hz), 7.00(1H, d, J=3.6 Hz),
7.69(1H, dd, J=6.3 and 8.4 Hz), 8.08(1H, d, J=3.6 Hz), 8.62 (1H, d,
J=6.3 Hz), 8.64(1H, d, J=8.4 Hz).
[1437] IR (KBr) cm.sup.-1: 3406, 2978, 1772, 1601, 1541, 1497,
1461, 1395, 1364, 1313, 1287, 1222, 1186, 1161, 1132, 1094, 1065,
1034.
[1438] MS(ESI): 675.sup.+(M+H.sup.+).
[1439] Elementary Analysis as
C.sub.27H.sub.27ClN.sub.8O.sub.7S.sub.2.mult-
idot.3.2H.sub.2O.multidot.0.45(C.sub.3H.sub.7OH).
[1440] Calculated: C, 44.81; H, 4.91; N, 14.75; Cl, 4.67; S, 8.44
(%). Found: C, 44.79; H, 4.97; N, 14.64; Cl, 4.61; S, 8.28 (%).
EXAMPLE 164
[1441] 220
[1442] .sup.1H-NMR (D.sub.2O) .delta.: 1.44(3H, d, J=7.2 Hz),
2.30(1H, m), 2.54(1H, m), 3.19 and 3.33(2H, ABq, J=18.0 Hz),
3.42-3.59(2H, m), 3.72-3.77(1H, m), 3.88-3.94 (1H, m), 4.65(1H, q,
J=7.2 Hz), 5.18(1H, d, J=4.8 Hz), 5.38(1H, m), 5.52 and 5.72(2H,
ABq, J=14.7 Hz), 5.88(1H, d, J=4.8 Hz), 7.00(1H, d, J=3.3 Hz),
7.69(1H, dd, J=6.0 and 8.4 Hz), 8.08(1H, d, J=3.3 Hz), 8.62(1H, d,
J=6.0 Hz), 8.65(1H, d, J=8.4 Hz).
[1443] IR (KBr) cm.sup.-1: 3397, 2982, 1773, 1602, 1540, 1497,
1462, 1395, 1364, 1316, 1287, 1186, 1132, 1092, 1064, 1034.
[1444] MS(ESI): 675.sup.+(M+H.sup.+).
[1445] Elementary Analysis as
C.sub.27H.sub.27ClN.sub.8O.sub.7S.sub.2.mult-
idot.5.0H.sub.2O.multidot.0.1(C.sub.3H.sub.7OH).
[1446] Calculated: C, 42.52; H, 4.94; N, 14.53; Cl, 4.60; S, 8.32
(%). Found: C, 42.54; H, 4.95; N, 14.29; Cl, 5.01; S, 8.09 (%).
EXAMPLE 165
[1447] 221
[1448] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=6.9 Hz),
1.76-1.89(1H, m), 2.08-2.18(1H, m), 2.98-3.52(5H, m), 3.18 and
3.37(2H, ABq, J=18.3 Hz), 4.55(2H, d, J=6.3 Hz), 4.65(1H, q, J=6.9
Hz), 5.18(1H, d, J=4.8 Hz), 5.55 and 5.70(2H, ABq, J=15.0 Hz),
5.86(1H, d, J=4.8 Hz), 7.04(1H, d, J=3.3 Hz), 7.70(1H, dd, J=6.3
and 8.1 Hz), 8.15(1H, d, J=3.3 Hz), 8.63(1H, d, J=8.1 Hz), 8.65(1H,
d, J=6.3 Hz).
[1449] IR (KBr) cm.sup.-1:3397, 2982, 1774, 1602, 1539, 1499, 1454,
1391, 1363, 1319, 1286, 1185, 1158, 1129, 1092, 1064, 1033.
[1450] MS(FAB): 689.sup.+(M+H.sup.+).
[1451] Elementary Analysis as
C.sub.28H.sub.29ClN.sub.8O.sub.7S.sub.2.mult- idot.4.9H.sub.2O.
[1452] Calculated: C, 43.26; H, 5.03; N, 14.41; Cl, 4.56; S, 8.25
(%). Found: C, 43.23; H, 5.01; N, 14.42; Cl, 4.47; S, 8.14 (%).
EXAMPLE 166
[1453] 222
[1454] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=6.9 Hz),
1.81-1.94(1H, m), 2.02-2.34(3H, m), 3.18 and 3.39(2H, ABq, J=17.7
Hz), 3.26-3.49(2H, m), 4.09-4.19(1H, m), 4.65(1H, q, J=6.9 Hz),
4.75(2H, brs), 5.18(1H, d, J=4.8 Hz), 5.57 and 5.71(2H, ABq, J=15.3
Hz), 5.86(1H, d, J=4.8 Hz), 7.10(1H, d, J=3.0 Hz), 7.74(1H, dd,
J=6.3 and 8.4 Hz), 8.17(1H, d, J=3.0 Hz), 8.66(1H, d, J=8.4 Hz),
8.69(1H, d, J=6.3 Hz).
[1455] IR (KBr) cm.sup.-1: 3396, 2982, 1775, 1602, 1540, 1501,
1465, 1391, 1364, 1287, 1186, 1158, 1131, 1092, 1064, 1033.
[1456] MS(FAB): 689.sup.+(M+H.sup.+).
[1457] Elementary Analysis as
C.sub.28H.sub.29ClN.sub.8O.sub.7S.sub.2.mult- idot.4.9H.sub.2O.
[1458] Calculated: C, 43.26; H, 5.03; N, 14.41; Cl, 4.56; S, 8.25
(%). Found: C, 43.54; H, 5.01; N, 14.32; Cl, 4.40; S, 7.96 (%).
EXAMPLE 167
[1459] 223
[1460] .sup.1H-NMR (D.sub.2O) .delta.: 1.44(3H, d, J=7.2 Hz),
2.02-2.31(2H, m), 3.18 and 3.40(2H, ABq, J=17.7 Hz), 3.30(1H, d,
J=12.9 Hz), 3.65(1H, dd, J=4.8 and 12.9 Hz), 4.37-4.50(1H, m),
4.66(1H, q, J=7.2 Hz), 4.63-4.74(1H, m), 4.86(2H, m), 5.19(1H, d,
J=5.1 Hz), 5.58 and 5.71(2H, ABq, J=15.0 Hz), 5.86(1H, d, J=5.1
Hz), 7.12(1H, d, J=3.3 Hz), 7.75(1H, dd, J=6.0 and 8.4 Hz),
8.19(1H, d, J=3.3 Hz), 8.67(1H, d, J=8.4 Hz), 8.69(1H, d, J=6.0
Hz).
[1461] IR (KBr) cm.sup.-1: 3395, 2984, 1774, 1603, 1539, 1502,
1465, 1392, 1364, 1322, 1287, 1221, 1186, 1132, 1091, 1066,
1034.
[1462] MS(FAB): 705.sup.+(M+H.sup.+).
[1463] Elementary Analysis as
C.sub.28H.sub.29ClN.sub.8O.sub.8S.sub.2.mult- idot.4.5H.sub.2O.
[1464] Calculated: C, 42.77; H, 4.87; N, 14.25; Cl, 4.51; S, 8.16
(%). Found: C, 42.69; H, 4.51; N, 14.46; Cl, 4.36; S, 8.04 (%).
EXAMPLE 168
[1465] 224
[1466] .sup.1H-NMR (D.sub.2O) .delta.: 1.39(3H, d, J=6.6 Hz),
1.43(3H, d, J=6.9 Hz), 3.18 and 3.38(2H, ABq, J=17.7 Hz), 3.99(1H,
q-like), 4.65(1H, q, J=6.9 Hz), 4.66(2H, t-like), 5.18(1H, d, J=4.8
Hz), 5.57 and 5.71(2H, ABq, J=15.0 Hz), 5.86(1H, d, J=4.8 Hz),
7.11(1H, d, J=3.0 Hz), 7.74(1H, dd, J=6.3 and 8.4 Hz), 8.14(1H, d,
J=3.0 Hz), 8.64(1H, d, J=8.4 Hz), 8.69(1H, d, J=6.3 Hz).
[1467] IR (KBr) cm.sup.-1:3397, 2983, 1773, 1597, 1539, 1502, 1466,
1395, 1364, 1325, 1289, 1181, 1112, 1063, 1033.
[1468] MS(FAB): 663.sup.+(M+H.sup.+).
[1469] Elementary Analysis as
C.sub.26H.sub.27ClN.sub.8O.sub.7S.sub.2.mult- idot.4.7H.sub.2O.
[1470] Calculated: C, 41.76; H, 4.91; N, 14.98; Cl, 4.74; S, 8.58
(%). Found: C, 41.81; H, 4.80; N, 14.92; Cl, 4.70; S, 8.59 (%).
EXAMPLE 169
[1471] 225
[1472] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.2 Hz),
2.31(2H, quintet, J=7.2 Hz), 2.91(3H, s), 3.17 and 3.37(2H, ABq,
J=17.7 Hz), 3.38(2H, t, J=7.2 Hz), 4.48(2H, t, J=7.2 Hz), 4.65(1H,
q, J=7.2 Hz), 5.18(1H, d, J=4.8 Hz), 5.56 and 5.69(2H, ABq, J=15.0
Hz), 5.85(1H, d, J=4.8 Hz), 7.05(1H, d, J=3.3 Hz), 7.69(1H, dd,
J=6.0 and 8.7 Hz), 8.14(1H, d, J=3.3 Hz), 8.59(1H, d, J=8.7 Hz),
8.64(1H, d, J=6.0 Hz).
[1473] IR (KBr) cm.sup.-1: 3373, 1774, 1600, 1540, 1498, 1457,
1392, 1363, 1321, 1286, 1184, 1127, 1082, 1033.
[1474] MS(FAB): 719.sup.+(M+H.sup.+).
[1475] Elementary Analysis as
C.sub.28H.sub.31ClN.sub.10O.sub.7S.sub.2.mul-
tidot.4.3H.sub.2O.
[1476] Calculated: C, 42.21; H, 5.01; N, 17.58; Cl, 4.45; S, 8.05
(%). Found: C, 42.28; H, 4.87; N, 17.55; Cl, 4.19; S, 7.84 (%).
EXAMPLE 170
[1477] 226
[1478] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.2 Hz), 3.17
and 3.38(2H, ABq, J=17.7 Hz), 3.22(2H, m), 3.69(2H, t, J=6.3 Hz),
3.81(2H, m), 4.65(1H, q, J=7.2 Hz), 4.83(2H, t, J=6.3 Hz), 5.18(1H,
d, J=4.8 Hz), 5.57 and 5.71(2H, ABq, J=15.0 Hz), 5.86(1H, d, J=4.8
Hz), 7.10(1H, d, J=3.3 Hz), 7.74(1H, dd, J=6.0 and 8.4 Hz),
8.16(1H, d, J=3.3 Hz), 8.64(1H, d, J=8.4 Hz), 8.69(1H, d, J=6.0
Hz).
[1479] IR (KBr) cm.sup.-1:3385, 1773, 1601, 1539, 1500, 1466, 1393,
1364, 1287, 1186, 1139, 1112, 1064, 1033.
[1480] MS(FAB): 693.sup.+(M+H.sup.+).
[1481] Elementary Analysis as
C.sub.27H.sub.29ClN.sub.8O.sub.8S.sub.2.mult- idot.2.9H.sub.2O.
[1482] Calculated: C, 43.51; H, 4.71; N, 15.03; Cl, 4.76; S, 8.60
(%). Found: C, 43.61; H, 4.80; N, 15.12; Cl, 4.48; S, 8.21 (%).
EXAMPLE 171
[1483] 227
[1484] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=7.2 Hz), 3.19
and 3.28 (2H, ABq, J=18.0 Hz), 4.64(1H, q, J=7.2 Hz), 5.15(1H, d,
J=4.8 Hz), 5.41 and 5.65(2H, ABq, J=15.0 Hz), 5.87(1H, d, J=4.8
Hz), 6.58(1H, d, J=3.3 Hz), 7.43(1H, dd, J=6.3 and 8.1 Hz),
7.90(1H, d, J=3.3 Hz), 8.37(1H, d, J=8.1 Hz), 8.40(1H, d, J=6.3
Hz).
[1485] IR (KBr) cm.sup.-1: 3468, 3144, 3116, 3099, 3080, 2980,
2951, 2924, 2870, 2341, 2276, 2256, 1934, 1891, 1754, 1618, 1580,
1499, 1449, 1429, 1365, 1345, 1309, 1237, 1227, 1208, 1187, 1159,
1114, 1054.
[1486] MS(FAB): 622.sup.+(M+H.sup.+).
[1487] Elementary Analysis as
C.sub.23H.sub.20ClN.sub.7O.sub.8S.sub.2.mult- idot.3.5H.sub.2O.
[1488] Calculated: C, 40.32; H, 3.97; N, 14.31; Cl, 5.17; S, 9.36
(%). Found: C, 40.38; H, 3.90; N, 14.23; Cl, 5.36; S, 9.25 (%).
EXAMPLE 172
[1489] 228
[1490] .sup.1H-NMR (D.sub.2O) .delta.: 1.44(3H, d, J=6.9 Hz), 3.18
and 3.37 (2H, ABq, J=17.4 Hz), 4.26(s, 3H), 4.65(1H, q, J=6.9 Hz),
5.18(1H, d, J=4.8 Hz), 5.55 and 5.71(2H, ABq, J=15.3 Hz), 5.88(1H,
d, J=4.8 Hz), 6.91(1H, d, J=3.6 Hz), 7.74(1H, dd, J=6.3 and 8.1
Hz), 8.31(1H, d, J=3.6 Hz), 8.65(1H, d, J=8.1 Hz), 8.68(1H, d,
J=6.3 Hz).
[1491] IR (KBr) cm.sup.-1:3410, 3134, 2941, 1778, 1674, 1614, 1537,
1457, 1364, 1234, 1211, 1188, 1155, 1120, 1058, 1034.
[1492] MS(ESI): 636.sup.+(M+H.sup.+).
[1493] Elementary Analysis as
C.sub.24H.sub.22ClN.sub.7O.sub.8S.sub.2.mult- idot.3.2H.sub.2O.
[1494] Calculated: C, 41.55; H, 4.13; N, 14.13; Cl, 5.11; S, 9.24
(%). Found: C, 41.62; H, 4.21; N, 14.26; Cl, 4.90; S, 9.08 (%).
[1495] Quaternary Salt Ester: 229
[1496] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.44(3H, d, J=6.9 Hz),
1.46(9H, s), 3.34 and 3.42(2H, Abq, J=18.0 Hz), 3.76(3H, s),
4.26(3H, s), 4.89(1H, q, J=6.9 Hz), 5.19(1H, d, J=5.1 Hz), 5.22 and
5.29(2H, Abq, J=11.7 Hz), 5.68 and 5.75(2H, Abq, J=15.3 Hz),
5.97(1H, dd, J=5.1 and 8.4 Hz), 6.82(1H, s), 6.89(2H, d, J=9.0 Hz),
6.95(1H, d, J=3.6 Hz), 7.20-7.42(12H, m), 7.84(1H, dd, J=6.0 and
8.1 Hz), 8.67(1H, d, J=6.0 Hz), 8.73(1H, d, J=3.6 Hz), 8.86(1H, d,
J=8.1 Hz), 9.76(1H, d, J=8.4 Hz), 12.1(brs).
[1497] IR (KBr) cm.sup.-1: 3394, 3131, 3091, 3061, 3031, 2978,
2937, 1789, 1719, 1632, 1613, 1549, 1515, 1495, 1455, 1391, 1368,
1247, 1176, 1154, 1119, 1063, 1032.
[1498] MS(FAB):
1222.sup.+(C.sub.50H.sub.49ClN.sub.7O.sub.11S.sub.2.sup.+)- .
EXAMPLE 173
[1499] 230
[1500] .sup.1H-NMR (D.sub.2O) .delta.: 1.47(3H, d, J=6.9 Hz),
2.43(3H, s), 3.26 and 3.62 (2H, ABq, J=17.7 Hz), 4.66(1H, q, J=6.9
Hz), 4.79 and 4.95(2H, ABq, J=14.7 Hz), 5.26(1H, d, J=4.8 Hz),
5.88(1H, d, J=4.8 Hz), 6.26(1H, s).
[1501] IR (KBr) cm.sup.-1:3312, 3190, 1776, 1671, 1617, 1535, 1460,
1392, 1337, 1187, 1134, 1100, 1064, 1034.
[1502] MS(FAB): 602.sup.+(M+H.sup.+).
[1503] Elementary Analysis as
C.sub.20H.sub.20ClN.sub.7O.sub.7S.sub.3.mult- idot.2.5H.sub.2O.
[1504] Calculated: C, 37.12; H, 3.89; N, 15.15; Cl, 5.48; S, 14.87
(%). Found: C, 36.94; H, 3.98; N, 14.93; Cl, 5.42; S, 15.09
(%).
EXAMPLE 174
[1505] 231
[1506] .sup.1H-NMR (D.sub.2O) .delta.: 1.44(3H, d, J=7.2 Hz), 3.26
and 3.66(2H, ABq, J=18.0 Hz), 4.64(1H, q, J=7.2 Hz), 5.25 and
5.50(2H, ABq, J=14.4 Hz), 5.28(1H, d, J=4.8 Hz), 5.89(1H, d, J=4.8
Hz), 6.78(1H, dd, J=1.8 and 3.0 Hz), 8.04(1H, d, J=1.8 Hz), 8.27
and 8.94(2H, ABq, J=7.2 Hz), 8.53(1H, d, J=3.0 Hz).
[1507] IR (KBr) cm.sup.-1: 3417, 3135, 1779, 1673, 1639, 1537,
1480, 1446, 1397, 1360, 1217, 1159, 1116, 1036.
[1508] MS(FAB): 633.sup.+(M+H.sup.+).
[1509] Elementary Analysis as
C.sub.24H.sub.21ClN.sub.8O.sub.7S.sub.2.mult- idot.2.7H.sub.2O.
[1510] Calculated: C, 42.29; H, 3.90; N, 16.44; Cl, 5.20; S, 9.41
(%). Found: C, 42.41; H, 3.97; N, 16.42; Cl, 4.93; S, 9.24 (%).
EXAMPLE 175
[1511] 232
[1512] .sup.1H-NMR (D.sub.2O) .delta.: 1.44(3H, d, J=6.9 Hz), 3.28
and 3.70(2H, ABq, J=18.0 Hz), 4.65(1H, q, J=6.9 Hz), 5.30(1H, d,
J=5.1 Hz), 5.36 and 5.63(2H, ABq, J=14.7 Hz), 5.92(1H, d, J=5.1
Hz), 8.07(1H, d, J=1.8 Hz), 8.59 and 9.18(2H, ABq, J=7.5 Hz),
8.85(1H, d, J=1.8 Hz).
[1513] IR (KBr) cm.sup.-1: 3415, 3132, 1778, 1673, 1638, 1530,
1475, 1341, 1247, 1186, 1159, 1125, 1095, 1064, 1032.
[1514] MS(FAB): 634.sup.+(M+H.sup.+).
[1515] Elementary Analysis as
C.sub.23H.sub.20ClN.sub.9O.sub.7S.sub.2.mult- idot.2.6H.sub.2O.
[1516] Calculated: C, 40.57; H, 3.73; N, 18.51; Cl, 5.21; S, 9.42
(%). Found: C, 40.61; H, 3.67; N, 18.52; Cl, 4.96; S, 9.20 (%).
EXAMPLE 176
[1517] 233
[1518] .sup.1H-NMR (D.sub.2O) .delta.: 2.30(2H, m), 2.67(3H, s),
3.0542H, m), 3.15 and 3.38 (2H, ABq, J=17.7 Hz), 4.52(2H, t, J=6.6
Hz), 4.55(2H, s), 5.17(1H, d, J=4.8 Hz), 5.56 and 5.67(2H, ABq,
J=15.0 Hz), 5.85(1H, d, J=4.8 Hz), 7.04(1H, d, J=3.3 Hz), 7.68(1H,
dd, J=6.3 and 8.1 Hz), 8.11(1H, d, J=3.3 Hz), 8.59(1H, d, J=8.1
Hz), 8.64(1H, d, J=6.3 Hz).
[1519] IR (KBr) cm.sup.-1: 3418, 1771, 1607, 1534, 1497, 1466,
1391, 1360, 1317, 1152, 1119, 1052, 1020.
[1520] MS(ESI): 707.sup.+(M+H.sup.+).
[1521] Elementary Analysis as
C.sub.26H.sub.27BrN.sub.8O.sub.7S.sub.2.mult- idot.5.4H.sub.2O.
[1522] Calculated: C, 38.80; H, 4.73; N, 13.92; Br, 9.93; S, 7.97
(%). Found: C, 38.80; H, 4.46; N, 14.04; Br, 9.66; S, 8.01 (%).
[1523] Quaternary Salt Ester: 234
[1524] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.40(9H, s), 1.46(18H,
s), 2.03(2H, m), 2.78(3H, brs), 3.18(2H, t, J=6.6 Hz), 3.26 and
3.43(2H, Abq, J=18.3 Hz), 3.75(3H, s), 4.43(2H, t-like), 4.55(2H,
s), 5.17(1H, d, J=4.8 Hz), 5.21 and 5.28(2H, Abq, J=11.7 Hz), 5.65
and 5.73(2H, ABq, J=15.0 Hz), 5.94(1H, dd, J=4.8 and 8.7 Hz), 6.88
and 7.32(4H, Abq, J=8.7 Hz), 7.00(1H, d, J=3.3 Hz), 7.79(1H, dd,
J=6.0 and 8.1 Hz), 8.43(1H, d, J=3.3 Hz), 8.60(1H, d, J=6.0 Hz),
8.88(1H, d, J=8.1 Hz), 9.61(1H, d, J=8.7 Hz), 12.1(brs).
[1525] IR (KBr) cm.sup.-1:3428, 3060, 2976, 2933, 1790, 1720, 1686,
1630, 1613, 1584, 1548, 1515, 1496, 1455, 1393, 1368, 1300, 1247,
1156, 1078, 1062, 1024.
[1526] MS(ESI):
1083.sup.+(C.sub.48H.sub.60BrN.sub.8O.sub.12S.sub.2.sup.+)- .
EXAMPLE 177
[1527] 235
[1528] .sup.1H-NMR (D.sub.2O) .delta.: 1.43(3H, d, J=6.9 Hz), 3.17
and 3.38(2H, ABq, J=17.7 Hz), 4.65(1H, q, J=6.9 Hz), 4.70-4.75(4H,
m), 5.18(1H, d, J=4.8 Hz), 5.57 and 5.71(2H, ABq, J=15.3 Hz),
5.86(1H, d, J=4.8 Hz), 5.95(1H, quintet-like), 7.20(1H, d, J=3.6
Hz), 7.73(1H, dd, J=6.3 and 8.4 Hz), 8.53(1H, d, J=3.6 Hz),
8.60(1H, d, J=8.4 Hz), 8.70(1H, d, J=6.3 Hz).
[1529] IR (KBr) cm.sup.-1: 3407, 2985, 2670, 1773, 1604, 1539,
1502, 1463, 1394, 1364, 1286, 1185, 1136, 1090, 1064, 1032.
[1530] MS(FAB): 661.sup.+(M+H.sup.+).
[1531] Elementary Analysis as
C.sub.26H.sub.25ClN.sub.8O.sub.7S.sub.2.mult- idot.4.5H.sub.2O.
[1532] Calculated: C, 42.08; H, 4.62; N, 15.10; Cl, 4.78; S, 8.64
(%). Found: C, 42.05; H, 4.60; N, 15.23; Cl, 4.50; S, 8.34 (%).
EXAMPLE 178
[1533] 236
[1534] .sup.1H-NMR (D.sub.2O) .delta.: 1.37(3H, d, J=6.9 Hz), 4.34
and 4.41(2H, ABq, J=17.4 Hz), 4.61(1H, q, J=6.9 Hz), 4.87 and
5.21(2H, ABq, J=14.7 Hz), 5.31(1H, d, J=3.9 Hz), 5.65(1H, d, J=3.9
Hz), 6.83 and 8.08(2H, ABq, J=7.2 Hz).
[1535] IR (KBr) cm.sup.-1: 3344, 3197, 1781, 1655, 1538, 1444,
1402, 1372, 1349, 1279, 1240, 1210, 1171, 1109, 1064, 1034.
[1536] MS(FAB): 566.sup.+(M+H.sup.+)
[1537] Elementary Analysis as
C.sub.21H.sub.20ClN.sub.7O.sub.8S.multidot.3- .0H.sub.2O.
[1538] Calculated: C, 40.68; H, 4.23; N, 15.81; Cl, 5.72; S, 5.17
(%). Found: C, 40.56; H, 3.90; N, 15.83; Cl, 5.84; S, 5.18 (%).
EXAMPLE 179
[1539] 237
[1540] .sup.1H-NMR (D.sub.2O) .delta.: 1.38(3H, d, J=7.2 Hz),
3.33(2H, t, J=6.0 Hz), 3.73(2H, t, J=6.0 Hz), 4.34 and 4.45(2H,
ABq, J=17.4 Hz), 4.63(1H, q, J=7.2 Hz), 4.78 and 5.32(2H, ABq,
J=14.7 Hz), 5.33(1H, d, J=3.9 Hz), 5.63(1H, d, J=3.9 Hz), 6.83(2H,
d-like), 8.08(2H, m).
[1541] IR (KBr) cm.sup.-1: 3396, 3067, 1779, 1649, 1601, 1556,
1448, 1403, 1371, 1350, 1279, 1217, 1171, 1107, 1063, 1033.
[1542] MS(FAB): 623.sup.+(M+H.sup.+).
[1543] Elementary Analysis as
C.sub.24H.sub.27ClN.sub.8O.sub.8S.multidot.4- .9H.sub.2O.
[1544] Calculated: C, 40.52; H, 5.21; N, 15.75; Cl, 4.98; S, 4.51
(%). Found: C, 40.36; H, 4.96; N, 15.90; Cl, 5.12; S, 4.67 (%).
EXAMPLE 180
[1545] 238
[1546] .sup.1H-NMR (D.sub.2O) .delta.: 1.31 (3H, d, J=7.2 Hz), 2.64
(3H, s), 3.03 (1H, d, J=17.1 Hz), 3.21 (2H, t, J=6.0 Hz), 3.45 (1H,
d, J=17.1 Hz), 3.61 (2H, t, J=6.0 Hz), 4.51 (1H, q, J=7.2 Hz), 4.76
(1H, d, J=15.0 Hz), 4.97 (1H, d, J=15.0 Hz), 5.10 (1H, d, J=4.2
Hz), 5.70 (1H, d, J=4.2 Hz), 6.81 (2H, d, J=6.3 Hz), 8.01-8.13 (2H,
m).
[1547] IR (KBr) cm.sup.-1: 3388, 3066, 1773, 1650, 1590, 1557,
1533, 1450, 1394, 1355, 1320, 1289, 1217, 1169, 1094, 1064,
1036.
[1548] MS(FAB): 623.sup.+(M+H.sup.+).
[1549] Elementary Analysis as
C.sub.24H.sub.27FN.sub.8O.sub.7S.sub.2.multi- dot.3.8H.sub.2O.
[1550] Calculated: C, 41.71; H, 5.05; N, 16.21; F, 2.75; S, 9.28
(%). Found: C, 41.69; H, 4.92; N, 16.23; F, 2.51; S, 9.05 (%).
EXAMPLE 181
[1551] 239
[1552] .sup.1H-NMR (D.sub.2O) .delta.: 1.52 (3H, d, J=6.9 Hz), 3.25
(1H, d, J=17.7 Hz), 3.63 (1H, d, J=17.7 Hz), 4.84 (1H, q, J=6.9
Hz), 4.88 (1H, d, J=14.7 Hz), 5.06 (1H, d, J=14.7 Hz), 5.26 (1H, d,
J=5.1 Hz), 5.87 (1H, d, J=5.1 Hz), 6.85 (1H, d, J=7.5 Hz), 8.21
(1H, dd, J=1.5, 7.5 Hz), 8.68 (1H, d, J=1.5 Hz).
[1553] IR (KBr) cm.sup.-1: 3397, 3198, 1776, 1659, 1539, 1494,
1445, 1391, 1372, 1238, 1169, 1103, 1065, 1037.
[1554] MS (FAB): 583 (M+H).sup.+, 1165 (2M+H).sup.+.
[1555] Elementary Analysis as
C.sub.20H.sub.19ClN.sub.8O.sub.7S.sub.2.mult- idot.2.1H.sub.2O.
[1556] Calculated: C, 38.69; H, 3.77; N, 18.05; Cl, 5.71; S, 10.33
(%). Found: C, 38.81; H, 3.70; N, 18.01; Cl, 5.54; S, 10.05
(%).
EXAMPLE 182
[1557] 240
[1558] .sup.1H-NMR (D.sub.2O) .delta.: 1.44 (3H, d, J=6.9 Hz), 3.16
(1H, d, J=17.7 Hz), 3.57 (1H, d, J=17.7 Hz), 4.21 (2H, m), 4.52
(2H, m), 5.11 (1H, d, J=14.4 Hz), 5.24 (1H, d, J=4.8 Hz), 5.86 (1H,
d, J=4.8 Hz), 6.89 (2H, m), 8.23 (2H, m).
[1559] IR (KBr) cm.sup.-1: 3399, 3059, 1772, 1649, 1601, 1551,
1445, 1361, 1288, 1217, 1167, 1095, 1065, 1035.
[1560] MS (FAB): 637 (M+H).sup.+, 1273 (2M+H).sup.+.
[1561] Elementary Analysis as
C.sub.24H.sub.25ClN.sub.8O.sub.7S.sub.2.mult- idot.2.2H.sub.2O.
[1562] Calculated: C, 42.60; H, 4.38; N, 16.56; Cl, 5.24; S, 9.48
(%). Found: C, 42.67; H, 4.31; N, 16.71; Cl, 5.16; S, 9.08 (%).
EXAMPLE 183
[1563] 241
[1564] .sup.1H-NMR (D.sub.2O) .delta.: 1.33 (3H, d, J=6.9 Hz), 2.62
(3H, s), 3.12 (1H, d, J=18.0 Hz), 3.22 (2H, t, J=5.7 Hz), 3.53 (1H,
d, J=18.0 Hz), 3.82 (2H, t, J=5.7 Hz), 4.54 (1H, q, J=6.9 Hz), 4.75
(1H, d, J=14.7 Hz), 4.96 (1H, d, J=14.7 Hz), 5.13 (1H, d, J=5.1
Hz), 5.74 (1H, d, J=5.1 Hz), 6.77 (1H, d, J=7.5 Hz), 8.12 (1H, br
d, J=7.5 Hz), 8.70 (1H, br s).
[1565] IR (KBr) cm.sup.-1: 3409, 1775, 1652, 1605, 1538, 1509,
1447, 1394, 1370, 1287, 1170, 1095, 1065, 1035.
[1566] MS (FAB): 640 (M+H).sup.+, 1279 (2M+H).sup.+.
[1567] Elementary Analysis as
C.sub.23H.sub.26ClN.sub.9O.sub.7S.sub.2.mult- idot.3.5H.sub.2O.
[1568] Calculated: C, 39.29; H, 4.73; N, 17.93; Cl, 5.04; S, 9.12
(%). Found: C, 39.43; H, 4.68; N, 17.74; Cl, 5.00; S, 8.95 (%).
EXAMPLE 184
[1569] 242
[1570] .sup.1H-NMR (D.sub.2O) .delta.: 1.45 (3H, d, J=6.9 Hz), 3.17
(1H, d, J=18.0 Hz), 3.24 (2H, t, J=5.1 Hz), 3.39 (2H, t, J=6.3 Hz),
3.57 (1H, d, J=18.0 Hz), 3.77 (2H, t, J=6.3 Hz), 3.85 (2H, t, J=5.1
Hz), 4.66 (1H, q, J=6.9 Hz), 4.88 (1H, d, J=15.0 Hz), 5.09 (1H, d,
J=15.0 Hz), 5.24 (1H, d, J=4.8 Hz), 5.86 (1H, d, J=4.8 Hz), 6.94
(2H, d, J=6.9 Hz), 8.19 (2H, m).
[1571] IR (KBr) cm.sup.-1: 3378, 1774, 1650, 1598, 1556, 1448,
1394, 1358, 1286, 1218, 1168, 1093, 1066, 1034.
[1572] MS (FAB): 669 (M+H).sup.+.
[1573] Elementary Analysis as
C.sub.25H.sub.29ClN.sub.8O.sub.8S.sub.2.mult- idot.2.7H.sub.2O.
[1574] Calculated: C, 41.83; H, 4.83; N, 15.61; Cl, 4.94; S, 8.93
(%). Found: C, 41.76; H, 4.61; N, 15.80; Cl, 4.78; S, 8.65 (%).
EXAMPLE 185
[1575] 243
[1576] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39 (3H, d, J=6.9 Hz),
2.21 (3H, brs), 2.97 and 3.48 (2H, ABqt, J=17.7 Hz), 4.57 (1H, q,
J=6.9 Hz), 5.09 (1H, d, J=4.8 Hz), 5.41 (2H, brs), 5.77 (1H, dd,
J=4.8, 8.4 Hz), 6.75 (1H, t-like), 7.37-7.39 (3H, m), 7.70 (2H,
brs), 8.05 (1H, d, J=5.4 Hz), 9.96 (1H, brs), 13.5 (1H, brs).
[1577] IR (KBr) cm.sup.-1: 3339, 3195, 1773, 1646, 1603, 1567,
1479, 1424, 1394, 1338, 1286, 1227, 1190, 1161, 1094, 1035.
[1578] MS(FAB): 635.sup.+(M+H).sup.+.
[1579] Elementary Analysis as
C.sub.24H.sub.23ClN.sub.8O.sub.7S.sub.2.mult- idot.2.3H.sub.2O.
[1580] Calculated: C, 42.61; H, 4.11; N, 16.56; Cl, 5.24; S, 9.48
(%). Found: C, 42.72; H, 4.27; N, 16.53; Cl, 5.02; S, 9.13 (%).
EXAMPLE 186
[1581] 244
[1582] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.54 (3H, d, J=7.5 Hz),
2.76 (3H, s), 3.24 and 3.46 (2H, ABqt, J=18.6 Hz), 3.51 (2H, t,
J=6.3 Hz), 4.56 (2H, t, J=6.3 Hz), 4.98 (1H, q, J=7.5 Hz), 5.27
(1H, d, J=4.8 Hz), 5.36 and 5.49 (2H, ABq, J=15.9 Hz), 5.91 (1H, d,
J=4.8 Hz), 7.11 (1H, dd, J=6.3, 7.8 Hz), 7.80 (1H, d, J=7.8 Hz),
7.95 (1H, d, J=6.3 Hz).
[1583] IR (KBr) cm.sup.-1: 3369, 2457, 1761, 1646, 1564, 1475,
1435, 1398, 1360, 1317, 1284, 1191, 1164, 1092, 1036.
[1584] MS(FAB): 678.sup.+(M+H).sup.+
[1585] Elementary Analysis as
C.sub.26H.sub.28ClN.sub.9O.sub.7S.sub.2.mult- idot.3.2H.sub.2O.
[1586] Calculated: C, 42.44; H, 4.71; N, 17.13; Cl, 4.82; S, 8.72
(%). Found: C, 42.15; H, 4.41; N, 17.15; Cl, 4.86; S, 8.68 (%).
EXAMPLE 187
[1587] 245
[1588] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=6.9 Hz),
2.16-2.24 (3H, m), 3.37 (1H, d, J=18.3 Hz), 3.43 (3H, s), 3.57-3.76
(4H, m), 4.31 (2H, t, J=8.1 Hz), 4.79 (1H, d, J=5.1 Hz), 4.99 (1H,
q, J=6.9 Hz), 5.49 and 5.68 (2H, ABq, J=15.0 Hz), 5.92 (1H, d,
J=5.1 Hz), 7.35 (1H, dd, J=6.6, 7.8 Hz), 7.97 (1H, d, J=7.8 Hz),
8.14 (1H, d, J=6.6 Hz).
[1589] IR (KBr) cm.sup.-1: 3378, 3183, 1773, 1650, 1565, 1495,
1441, 1395, 1352, 1316, 1287, 1223, 1165, 1095, 1034.
[1590] MS(FAB): 723.sup.+(M+H).sup.+
[1591] Elementary Analysis as
C.sub.27H.sub.31ClN.sub.10O.sub.8S.sub.2.mul-
tidot.2.6H.sub.2O.
[1592] Calculated: C, 42.11; H, 4.74; N, 18.19; Cl, 4.60; S, 8.33
(%). Found: C, 42.14; H, 4.54; N, 18.19; Cl, 4.50; S, 8.16 (%).
EXAMPLE 188
[1593] 246
[1594] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39 (3H, d, J=6.9 Hz),
3.07 and 3.49 (2H, d, J=17.7 Hz), 4.56 (1H,q, J=6.9 Hz), 4.92 and
5.38 (2H, ABq, J=13.5 Hz), 5.07 (1H, d, J=5.4 Hz), 5.73 (1H, dd,
J=5.4, 9.0 Hz), 7.35 (1H, d, J=3.3 Hz), 7.40 (2H, brs), 7.54 (1H,
d, J=3.3 Hz), 8.05 (2H, brs), 8.90 (2H, brd, J=7.2 Hz), 9.70 (1H,
brs).
[1595] IR (KBr) cm.sup.-1: 3416, 2984, 1777, 1643, 1547, 1515,
1476, 1461, 1348, 1204, 1161, 1102, 1063, 1036.
[1596] MS(FAB): 665.sup.+(M+H).sup.+.
[1597] Elementary Analysis as
C.sub.24H.sub.21ClN.sub.8O.sub.7S.sub.3.mult- idot.2.5H.sub.2O.
[1598] Calculated: C, 40.59; H, 3.69; N, 15.78; Cl, 4.99; S, 13.55
(%). Found: C, 40.41; H, 3.62; N, 16.01; Cl, 5.03; S, 13.25
(%).
EXAMPLE 189
[1599] 247
[1600] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.54 (3H, d, J=6.9 Hz),
2.14-2.24 (2H, m), 2.71 (3H, s), 3.11 (2H, t, J=8.4 Hz), 3.25 and
3.48 (2H, ABqt, J=18.3 Hz), 4.28 (2H, t, J=7.5 Hz), 4.99 (1H, q,
J=6.9 Hz), 5.29 (1H, d, J=4.8 Hz), 5.34 and 5.51 (2H, ABq, J=15.6
Hz), 5.91 (1H, d, J=4.8 Hz), 7.08 (1H, dd, J=6.6, 7.5 Hz), 7.78
(1H, d, J=7.5 Hz), 7.91 (1H, d, J=6.6 Hz).
[1601] IR (KBr) cm.sup.-1: 3341, 3177, 1772, 1646, 1564, 1473,
1439, 1394, 1346, 1284, 1190, 1162, 1092, 1058, 1034.
[1602] MS(FAB): 692.sup.+(M+H).sup.+.
[1603] Elementary Analysis as
C.sub.27H.sub.30ClN.sub.9O.sub.7S.sub.2 3.8H.sub.2O.
[1604] Calculated: C, 42.63; H, 4.98; N, 16.57; Cl, 4.66; S, 8.43
(%). Found: C, 42.69; H, 4.81; N, 16.49; Cl, 4.67; S, 8.51 (%).
EXAMPLE 190
[1605] 248
[1606] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.55 (3H, d, J=6.9 Hz),
3.27 (2H, t, J=8.3 Hz), 3.36 and 3.59 (2H, ABq, J=18.3 Hz), 3.61
(2H, t, J=6.8 Hz), 3.86 (2H, t, J=8.3 Hz), 4.98 (1H, sept, J=6.9
Hz), 5.27 (1H, d, J=4.8 Hz), 5.47 and 5.70 (2H, ABq, J=15.2 Hz),
7.32-7.38 (1H, m), 8.01 (1H, d, J=7.5 Hz), 8.16 (1H, d, J=6.9
Hz).
[1607] IR (KBr) cm.sup.-1: 3371, 3184, 1772, 1667, 1603, 1563,
1395, 1351, 1316, 1222, 1170, 1072, 1034, 984, 867, 758.
[1608] MS(FAB): 709.sup.+(M+H).sup.+.
[1609] Elementary Analysis as
C.sub.26H.sub.29ClN.sub.10O.sub.8S.sub.2.mul-
tidot.2.6H.sub.2O.
[1610] Calculated: C, 41.31; H, 4.56; N, 18.53; Cl, 4.69; S, 8.48
(%). Found: C, 41.22; H, 4.37; N, 18.51; Cl, 5.27; S, 8.25 (%).
EXAMPLE 191
[1611] 249
[1612] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.39 (3H, d, J=6.9 Hz),
3.04 and 3.486 (2H, ABqt, J=17.4 Hz), 3.67 (2H, t, J=5.4 Hz), 4.07
(2H, t, J=5.4 Hz), 4.57 (1H, q, J=6.9 Hz), 4.84 and 5.30 (2H, ABq,
J=13.8 Hz), 5.06 (1H, d, J=4.8 Hz), 5.72 (1H, dd, J=4.8, 8.7 Hz),
6.31 (1H, d, J=1.8 Hz), 7.14 (2H, brs), 7.41 (2H, brs), 7.57 (1H,
d, J=1.8 Hz), 8.72 (1H, d, J=7.2 Hz), 9.65 (1H, brs), 10.8 (1H,
brs).
[1613] IR (KBr) cm.sup.-1: 3308, 2948, 1777, 1648, 1608, 1541,
1456, 1357, 1212, 1165, 1109, 1065, 1036.
[1614] MS(FAB): 692.sup.+(M+H).sup.+.
[1615] Elementary Analysis as
C.sub.26H.sub.26ClN.sub.9O.sub.8S.sub.2.mult- idot.2.2H.sub.2O.
[1616] Calculated: C, 42.68; H, 4.19; N, 17.23; Cl, 4.84; S, 8.78
(%). Found: C, 42.79; H, 4.10; N, 17.32; Cl, 4.47; S, 8.45 (%).
EXAMPLE 192
[1617] 250
[1618] .sup.1H-NMR (d.sub.6-DMSO) .delta.: 1.20 (3H, t, J=6.9 Hz),
1.38 (3H, d, J=7.2 Hz), 2.94 and 3.27 (2H, ABqt, J=17.4 Hz), 4.16
(2H, q, J=6.9 Hz), 4.55 (2H, q, J=7.2 Hz), 5.00 (1H, d, J=4.8 Hz),
5.22 and 5.34 (2H, ABq, J=14.4 Hz), 5.68 (1H, dd, J=4.8, 9.0 Hz),
6.05 (1H, s), 6.99 (1H, dd, J=6.6, 7.5 Hz), 7.40 (2H, brs), 7.79
(1H, d, J=7.5 Hz), 7.88 (2H, brs), 8.27 (1H, d, J=6.6 Hz), 9.78
(1H, brs).
[1619] IR (KBr) cm.sup.-1: 3346, 3189, 2985, 2936, 1777, 1646,
1594, 1563, 1474, 1441, 1386, 1342, 1285, 1191, 1162, 1098,
1036.
[1620] MS(FAB): 649.sup.+(M+H).sup.+.
[1621] Elementary Analysis as
C.sub.25H.sub.25ClN.sub.8O.sub.7S.sub.2.mult- idot.2.3H.sub.2O.
[1622] Calculated: C, 43.48; H, 4.32; N, 16.23; Cl, 5.13; S, 9.29
(%). Found: C, 43.48; H, 4.21; N, 16.28; Cl, 4.80; S, 8.98 (%).
EXAMPLE 193
[1623] 251
[1624] .sup.1H NMR (d.sub.6-DMSO) .delta.: 1.04 (3H, t, J=7.2 Hz),
1.40 (3H, d, J=6.9 Hz), 2.60-2.70 (2H, m), 2.97 and 3.49(2H, ABqt,
J=17.4 Hz), 4.57 (1H, q, J=6.9 Hz), 5.10 (1H, d, J=4.8 Hz), 5.24
and 5.46 (2H, ABq, J=14.7 Hz), 5.78 (1H, dd, J=4.8, 8.1 Hz), 6.75
(1H, t-like), 7.37-7.39 (3H, m), 7.72 (2H, brs), 8.00 (1H, brs),
9.92 (1H, brs), 13.1 (1H, brs).
[1625] IR (KBr) cm.sup.-1: 3341, 3196, 2972, 2934, 1176, 1633,
1567, 1475, 1423, 1344, 1225, 1187, 1159, 1101, 1058, 1033.
[1626] MS(FAB): 649.sup.+(M+H).sup.+.
[1627] Elementary Analysis as
C.sub.25H.sub.25ClN.sub.8O.sub.7S.sub.2.mult- idot.2.6H.sub.2O.
[1628] Calculated: C, 43.15; H, 4.37; N, 16.10; Cl, 5.09; S, 9.21
(%). Found: C, 43.25; H, 4.18; N, 16.06; Cl, 4.81; S, 8.86 (%).
EXAMPLE 194
[1629] 252
[1630] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.41 (3H, d, J=6.3 Hz),
1.54 (3H., d, J=6.9 Hz), 3.26 and 3.49 (2H, ABqt, J=18.3 Hz),
3.87-3.99 (1H, m), 4.35-4.49 (2H, m), 5.29 (1H, d, J=4.8 Hz), 5.36
and 5.53 (2H, ABq, J=15.3 Hz), 5.91 (1H, d, J=4.8 Hz), 7.11 (1H,
dd, J=6.3, 7.8 Hz), 7.83 (1H, d, J=7.8 Hz), 7.95 (1H, d, J=6.3
Hz).
[1631] IR (KBr) cm.sup.-1: 3353, 3176, 1756, 1647, 1561, 1436,
1398, 1355, 1318, 1284, 1236, 1165, 1092, 1036.
[1632] MS(FAB): 678.sup.+(M+H).sup.+.
[1633] Elementary Analysis as
C.sub.26H.sub.29ClN.sub.9O.sub.7S.sub.2.mult- idot.3.2H.sub.2O.
[1634] Calculated: C, 42.38; H, 4.84; N, 17.11; Cl, 4.81; S, 8.70
(%). Found: C, 42.46; H, 4.69; N, 17.11; Cl, 4.58; S, 8.47 (%).
EXAMPLE 195
[1635] 253
[1636] .sup.1H-NMR (D.sub.2O+DCl) .delta.: 1.54 (3H, d, J=6.9 Hz),
2.24 (3H, s), 2.26 (2H, d-like), 2.62-2.74 (2H, m), 3.19-3.34 (3H,
m), 3.46 (1H, d, J=18.3 Hz), 3.72 (2H, d-like), 4.69-4.78 (1H, m),
4.99 (1H, q, J=6.9 Hz), 5.29 (1H, d, J=4.8 Hz), 5.35 and 5.53 (2H,
ABq, J=15.6 Hz), 5.91 (1H, t-like), 7.08 (1H, t-like), 7.94 (2H,
t-like).
[1637] IR (KBr) cm.sup.-1: 3355, 3184, 1771, 1594, 1559, 1476,
1434, 1395, 1349, 1317, 1283, 1188, 1166, 1066, 1033, 1001.
[1638] MS(FAB): 704.sup.+(M+H).sup.+.
[1639] Elementary Analysis as
C.sub.28H.sub.30ClN.sub.9O.sub.7S.sub.2.mult- idot.3.6H.sub.2O.
[1640] Calculated: C, 43.73; H, 4.88; N, 16.39; Cl, 4.61; S, 8.34
(%). Found: C, 43.74; H, 4.65; N, 16.50; Cl, 4.40; S, 8.13 (%).
EXAMPLE A
[1641] According to the above Examples, the following compound (I)
is synthesized. 254255256257
Experiment 1
[1642] The MIC (minimum inhibitory concentration) value of the
invention compounds against various bacterial was determined by the
usual agar dilution method. The result is shown in Table 1.
3 TABLE 1 (unit: .mu.g/ml) Exam- S. aureus S. epidermidis E.
cloacae ple SR3637 SR25009 SR4321 P. aeruginosa No (H-MRSA) *1
(MRSE) *2 (Bla++) *3 SR24-12 *3 Ref. 1 >128 >128 64 64 Ex. 1
64 32 16 8 Ex. 3 32 32 16 8 Ex. 4 16 8 4 8 Ex. 5 16 8 8 -- Ex. 8 32
32 4 4 Ex. 9 16 8 2 4 Ex. 18 8 4 2 4 Ex. 19 16 8 1 8 Ex. 20 16 16 8
4 Ex. 79 8 8 2 4 Ex. 98 8 8 2 2 Ex. 124 16 8 4 4 Ex. 132 16 8 4 4
*1 Methicillin High-Resistant Staphylococcus Aureus *2 Methicillin
High-Resistant Staphylococcus Epidermidis *3 AmpC High-Production
Cephem Resistant Strain
[1643] Ref 1 258
[1644] The above result shows that the invention compounds, having
a substituent such as halogen on the aminothiazole ring, possesses
a potent antibacterial activity against various bacteria including
H-MRSA, H-MRSE and P. aeruginosa in comparison with Ref 1 compound,
Ceftazidime.
Formulation Example 1
[1645] The invention compound of Example 1 and a pH adjusting agent
are filled as powder to prepare an injection agent.
Industrial Utility
[1646] The invention compounds exhibit a potent antibacterial
activity against various bacteria including Gram-positive bacteria
and Gram-negative bacteria. In particular, the invention compounds
are stable against .beta.-lactamase and extremely efficatious
against cephem-resistant bacteria including C-class
.beta.-lactamase-producing P. aeruginosa. Further, the invention
compounds have an excellent pharmacokinetics and a high
water-solubility, thus preferably being suitable for an injection
agent.
* * * * *